RESUMO

This dataset features 200 sagittal projection images derived from Cone Beam Computed Tomography (CBCT) scans, corrected according to the Natural Head Position (NHP) guidelines proposed by Fredrik Lundström and Anders Lundström. The images originate from orthodontic patients in Cali, Valle del Cauca, Colombia, encompassing both initial phases and ongoing treatments. The dataset is divided into two groups: 100 images from female subjects (CoF) and 100 from male subjects (CoM), facilitating gender-specific studies. The dataset is accompanied by an Excel file ``Data info.xlsx'' that details the rotation angles in the axial (Yaw), coronal (Roll), and sagittal (Pitch) planes, along with the pixel size and image dimensions. This detailed documentation supports the replication of studies and aids in the interpretation of cephalometric analyses. Corrections made to align the images with NHP standards involve adjustments in the three main anatomical planes using points from the frontozygomatic suture (Fz) in the axial and coronal planes, and sella (S) and nasion (N) for the sagittal plane.

RESUMO

In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%-13% are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N-acetyltransferase-2 (NAT2) and cytochrome P450 2E1 (CYP2E1). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of NAT2 and CYP2E1 genotypes in native and mestizo population. An analytical cross-sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. NAT2 metabolizer was determined as fast, intermediate and slow, and CYP2E1 genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 NAT2 haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent NAT2*5B and NAT2*7B haplotypes were associated with DILI risk; while in natives, NAT2*5G and NAT2*13A haplotypes were associated with decreased risk of DILI. For CYP2E1, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of NAT2 single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for NAT2 was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between NAT2 and CYP2E alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.

Assuntos

Antituberculosos , Arilamina N-Acetiltransferase , Doença Hepática Induzida por Substâncias e Drogas , Citocromo P-450 CYP2E1 , Isoniazida , Tuberculose , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antituberculosos/uso terapêutico , Antituberculosos/efeitos adversos , Arilamina N-Acetiltransferase/genética , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas/genética , Estudos Transversais , Citocromo P-450 CYP2E1/genética , Genótipo , Indígenas Sul-Americanos/etnologia , Indígenas Sul-Americanos/genética , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Peru , Farmacogenética , Tuberculose/genética , Tuberculose/tratamento farmacológico , Grupos Raciais

RESUMO

Introduction: Metastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies. Methods: We sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing. Results: Overall, we found 22 variants -9 of them reported for the first time- and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort. Discussion: Our results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population.

RESUMO

BACKGROUND/AIM: Enzymatic variants involved in fluoropyrimidine metabolism have been associated with adverse events (AEs). We assessed the association between C677T (rs1801133) and A1298 (rs1801131) methylenetetrahydrofolate reductase (MTHFR) polymorphisms and AEs in patients with first-line fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Fifty patients with metastatic colorectal cancer were prospectively followed-up during the first 4 cycles of fluoropyrimidine-based treatment to assess AEs. Germline DNA was analyzed to determine the C677T and A1298C MTHFR polymorphisms. The associations between MTHFR polymorphisms and toxicity were examined. RESULTS: Individuals carrying at least one mutant allele of the MTHFR C677T polymorphism had increased risk to experience anemia (OR=1.69, 95% CI=1.13-2.53, p=0.005), neutropenia (OR=2.27, 95% CI=1.47-3.42, p<0.001) thrombocytopenia (OR=1.91, 95% CI=1.30-2.70, p<0.001), neuropathy (OR=1.77, 95% CI=1.16-2.70, p=0.02), diarrhea (OR=1.69, 95% CI=1.13-2.53, p=0.005), and hand-foot syndrome (OR=1.56, 95% CI=1.08-2.27, p=0.013), compared to patients carrying the wild type alleles. The presence of the mutant allele C of the MTHFR A1298C polymorphism was associated with increased risk of anemia (OR=2.75, 95% CI=1.01-7.48, p=0.02) and thrombocytopenia (OR=3.14, 95% CI=1.01-9.78, p=0.03); however, the prevalence of this allele in the sample was quite low (20%). CONCLUSION: MTHFR C677T and A1298C polymorphisms predicted toxicity in a subset of Mestizo patients with colorectal adenocarcinoma.

Assuntos

Antimetabólitos Antineoplásicos/toxicidade , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Etnicidade/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Idoso , Neoplasias Colorretais/patologia , Costa Rica , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Estudos Prospectivos

RESUMO

BACKGROUND: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. METHODS: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. RESULTS: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. CONCLUSIONS: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

Assuntos

Doença da Artéria Coronariana , Lipoproteína(a)/genética , Polimorfismo Genético , Calcificação Vascular/genética , Adulto , Idoso , Estudos Transversais , Variação Genética , Humanos , México , Pessoa de Meia-Idade , Grupos Raciais

RESUMO

ABSTRACT Background: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. Methods: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. Results: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. Conclusions: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

Assuntos

Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Polimorfismo Genético , Doença da Artéria Coronariana , Lipoproteínas/genética , Variação Genética , Estudos Transversais , Grupos Raciais , Calcificação Vascular/genética , México

RESUMO

The presence of germline and somatic deleterious mutations in the BRCA1 and BRCA2 genes has important clinical consequences for breast cancer (BC) patients. Analysis of the mutational status in BRCA genes is not yet common in public Latin American institutions; thus, our objective was to implement high-performance technology with highly reliable results with the possibility of analyzing several patients simultaneously, therefore reducing cost and work time. A prospective cohort of 252 unrelated sporadic breast cancer patients from the Mexican-mestizo population were analyzed using next generation sequencing (NGS) based on ion semiconductor sequencing. We found 28 pathogenic mutations (25 in BRCA1 and 13 in BRCA2), 11 of which had not been reported previously in Hispanic or Latin American populations. A total of 38 patients were positive for a pathogenic mutation representing 15% of our Mexican women cohort with breast cancer; 25 for BRCA1; and 13 for BRCA2. Our results revealed that there are mutations not analyzed by mutations panels, and our findings support the suitability of massive sequencing approaches in the public institutions of developing countries. Hence, BRCA screening should be offered to patients with breast cancer regardless of their family history of cancer in order to identify unaffected family carriers.

RESUMO

BACKGROUND: Tamoxifen metabolism is translated into four genetic phenotypes (GP): genetic poor metabolizer (gPM); genetic intermediate metabolizer (gIM); genetic normal metabolizer (gNM); and genetic ultra-rapid metabolizer (gUM). Although CYP2D6 is involved in tamoxifen biotransformation, its association with tamoxifen side effects (TSE) is limited. Therefore, we evaluated CYP2D6 GP and clinical variables as potential predictors of TSE in Mexican Mestizo patients. METHODS: This cross-sectional study evaluated CYP2D6 GP, clinical data, and self-reported TSE in 71 women. Potential predictors were tested in uni- and multivariable models. RESULTS: Hot flashes (57.75%), arthralgia (45.07%), headache (43.66%), and cramps (39.44%) were the most frequent TSE. Three GP were identified: gPM (2.8%); gNM (93.0%); and gUM (4.2%). In the univariate analysis, none of the GP was predictive of TSE. However, the uni- and multivariable models showed contraceptive use and chemotherapy treatment prior to tamoxifen therapy to be predictive. Two alleles were identified for the first time at unusually high frequencies: CYP2D6*34 (13.2%); and *39 (14.7%). CONCLUSIONS: Our findings indicate that CYP2D6 GP were not significantly predictive of TSE, though two clinical descriptors were. The present results are a valuable contribution to pharmacogenetic characterization of Mexican Mestizo populations who, like other Latin-American groups, are poorly represented in the literature.

RESUMO

BACKGROUND: Primary Osteoarthritis (OA) of the knee is a multifactorial disease that has an important genetic component, and several genes have been associated with its development. The vitamin D receptor has a role in skeletal metabolism that suggests a relationship with OA. The aim of this study was to analyze the association of Vitamin D receptor gene (VDR) polymorphisms in Mexican Mestizo patients. METHODS: A case-control study was conducted in which 107 cases with primary OA of the knee and 114 controls were included. Cases were patients > 40 years of age with a Body mass index (BMI) of ≤27 and a radiological score for OA of the knee of ≥2. Controls were subjects > 40 years of age with a radiological score of < 2. VDR polymorphisms rs1544410, rs7975232, and rs731236 were analyzed by means of restriction endonucleases, and logistic regression was developed to evaluate risk magnitude. RESULTS: A significantly increased risk was found of nearly two-fold for the allele T and TT genotypes of rs731236, independently of other well recognized risk factors. CONCLUSIONS: The rs731236 polymorphism is associated with the risk of primary OA of the knee in Mexican Mestizo population.

Assuntos

Osteoartrite do Joelho/genética , Polimorfismo Genético/genética , Receptores de Calcitriol/genética , Adulto , Alelos , Índice de Massa Corporal , Estudos de Casos e Controles , Etnicidade/genética , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , América Latina , Modelos Logísticos , Masculino , México/etnologia , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem

RESUMO

INTRODUCTION: There are no reports of the density of hair follicles in the scalp of Mexican mestizo population, necessitating the determination of normal references values for this population compared with other ethnic groups. OBJECTIVE: To determine the average hair follicle count on the scalp in Mexican mestizo population. MATERIALS AND METHODS: A total of 50 scalp samples (25 men and 25 women) from Mexican mestizo individuals aged between 19 and 60 years, with no clinical evidence of hair disease, obtained by biopsy punch at General Hospital "Dr. Manuel Gea González" were collected over 2 years. The total follicular density, vellus and terminal hair follicles, and the percentage in anagen and catagen-telogen phase were measured. χ2 was used as the basic statistical test. RESULTS: The mean number of total hair follicles in our Mexican mestizo population was 23.2 ± 4.2, which is lower compared with Thais, Iranians, and Caucasians. However, the ratio of terminal and vellus hair follicles was higher than in Thais, Caucasians, and African-Americans. The percentage of terminal hairs in anagen phase was lower than in the other populations, and higher in telogen, without exceeding 15%, established as the normal reference value. There was an association between sex and terminal hairs in telogen phase (p < 0.05). The average follicular density per mm2 was slightly higher compared with African-Americans and Asians. Women had more terminal hairs than men. CONCLUSIONS: The density of total follicles is lower in the Mexican mestizo population compared with Iranians, Thais, and Caucasians. However, the greater number of terminal hairs compared to vellus hairs gives the appearance of greater overall volume. The results of this study can be used as a reference for diseases of the scalp in the Mexican population.

RESUMO

Myotonic dystrophy type 1 is caused by expansion of a CTG trinucleotide repeat situated in the DMPK gene. Worldwide genetic studies suggest a single or limited number of mutational events cause the disease. However, distribution of CTG alleles and disease incidence varies among ethnicities. Due to the great ethnic diversity of the Mexican population, the present study was aimed at analyzing the impact of different lineages in shaping the CTG-repeat allelic distribution in the contemporary Mexican-Mestizo population as well as to shed light on the DM1 ancestral origin. Distribution of CTG-repeat alleles was similar among Mestizo and Amerindian subpopulations with (CTG)11-13 being the most frequent alleles in both groups, which implies that Mexican-Mestizo allelic distribution has been modeled by Amerindian ancestry. We diagnosed a relatively high number of cases, consistent with the high frequency of large-normal alleles found in Mexican subpopulations. Haplotype analysis using various polymorphic-markers in proximity to DMPK gene indicates that a single founder mutation originates myotonic dystrophy type 1 in Mexico; however, Y-STR haplogroups data and the presence of pre-mutated and large normal alleles in Amerindians support the hypothesis that both European and Amerindian ancestral chromosomes might have introduced the disease to the Mexican population, which was further disseminated through mestizaje.

Assuntos

Frequência do Gene/genética , Indígenas Norte-Americanos/genética , Distrofia Miotônica/etnologia , Distrofia Miotônica/genética , Miotonina Proteína Quinase/genética , Expansão das Repetições de Trinucleotídeos/genética , População Branca/genética , Efeito Fundador , Humanos , México/etnologia

RESUMO

BACKGROUND AND AIMS: Adiponectin (ADPN) is a cardioprotective adipocytokine, and its association with atherosclerosis development is controversial. The aim of the present study was to assess the association of low ADPN plasma levels with the presence of subclinical atherosclerosis in a Mexican-Mestizo population without history of diabetes or coronary artery disease (CAD). METHODS: In 818 subjects (53.4 ± 9 years; 49.9% women) anthropometry, subcutaneous and visceral adipose tissue, lipids, glucose, C-reactive protein (CRP), insulin, and ADPN levels were determined. Carotid artery intima-media thickness (CIMT) was measured with ultrasound in B mode and the sex-age specific value higher than 75th percentile defined the presence of subclinical atherosclerosis. Low ADPN was considered when plasma concentrations were lower than 25th percentile (8.67 µg/mL in women, 5.30 µg/mL in men). RESULTS: Prevalence of low ADPN was 43.6% (42.9% in women and 44.4% in men; p = 0.66) and elevated CIMT (eCIMT) was 23.8% (25.8% in women and 21.9% in men; p = 0.184). In addition to their higher prevalence of low ADPN, subjects with eCIMT had higher values of body mass index, blood pressure, total cholesterol, triglycerides, glucose, insulin, and CRP. Multivariate analysis revealed that independent of these factors, low ADPN was associated with eCIMT (OR [95% CI]: 1.505 [1.051-2.153]). CONCLUSIONS: In the studied population, low adiponectin concentrations are associated with a higher prevalence of subclinical atherosclerosis, independent of traditional cardiovascular risk factors.

Assuntos

Adiponectina/sangue , Aterosclerose/sangue , Adulto , Aterosclerose/epidemiologia , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Prevalência , Fatores de Risco

RESUMO

BACKGROUND: Asporin is a novel extracellular matrix protein (ECM) with an important role in the development of osteoarthritis (OA), because it has been reported that functional polymorphisms in the aspartic acid repeat (D) of the asporin gene (ASPN) are associated with susceptibility to OA. AIM: This study was planned to investigate the association of the ASPN polymorphism with primary OA of the knee in a Mexican population, including several countryside regions. METHODS: We conducted a case-control study in which 93 cases with primary OA of the knee and 118 controls were included. Cases included patients > 40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee of ≥ 2. Controls were subjects > 40 years of age with a radiologic score of < 2. The D repeat polymorphism was genotyped and logistic regression was developed to evaluate risk magnitude. RESULTS: The D14 allele was more common in our cases and was associated with an increased risk for developing OA, while the frequencies of the remaining alleles did not exhibit differences. CONCLUSION: Our data suggest that the D14 allele of the ASPN polymorphism could exert an influence on primary OA of the knee etiology in a Mexican Mestizo population.

Assuntos

Proteínas da Matriz Extracelular/genética , Indígenas Norte-Americanos/genética , Osteoartrite do Joelho/genética , Polimorfismo Genético , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/etnologia , Fenótipo , Sequências Repetitivas de Aminoácidos , Fatores de Risco

RESUMO

AIMS: Polymorphisms in the CYP2C9 and CYP2C19 genes confer potential risk for specific adverse drug reactions and therapeutic effect failure. Their frequencies differ among ethnic groups. This study was aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mestizo populations from Western Mexico and their comparison with the reported data from other ethnic groups. METHODS: The CYP2C alleles (CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3) were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analyses using DNA samples from 477 healthy Mestizo individuals of Colima (n = 100), Jalisco (n = 147), Michoacán (n = 117), and Nayarit (n = 113). RESULTS: Frequencies ranged from 2.2-3.0% and 4.8-8.9% for CYP2C9*3 and CYP2C9*2 alleles, respectively, and 5.4-12.0% for CYP2C19*2, whereas the CYP2C19*3 allele was not found. Haplotype GACA, which harbors the loss-of-function allele CYP2C19*2, was the second most frequent (8.7%). Genetic heterogeneity between the Western Mexican populations studied here and the global population was evident (p < 0.05), except for most American populations and other Mexican Mestizo populations. CONCLUSION: Our findings increase the evidence for genetic variability at relevant pharmacogenetic loci and could be useful in association studies involving drugs that are substrates for CYP2C enzymes in the Western Mexican population.

Assuntos

Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Indígenas Norte-Americanos/genética , Adulto , Alelos , Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Etnicidade/genética , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Haplótipos , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único

RESUMO

BACKGROUND: The HLA complex involved is a factor in the pathogenesis of leukemia. OBJECTIVES: The presence of class II HLA alleles DRB1 *, DQB1 *, DPA1 *, and DPB1 * was evaluated in 47 patients with acute lymphoblastic leukemia (ALL) and 48 with chronic myeloid leukemia (CML) for comparison with 48 healthy volunteers in Zulia, Venezuela, and to evaluate potential associations of HLA with leukemia. METHODS: Low- and high-resolution PCR-SSP was used for class II HLA regions DRB1 *, DQB1 *, DPA1 *, and DPB1 * following the instructions of KIT Olerup SSP Genovision. RESULTS: Alleles HLA-DRB1*14, especially DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, and the haplotypes HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 were associated with CML (RR > 3); alleles HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 and the haplotypes HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 were protective (RR < 1). Alleles HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 had a positive association with ALL. Alleles HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 and the haplotypes HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 were negatively associated. CONCLUSIONS: The other association patterns identified suggest marked differences in the pathogenesis of leukemia, which suggests possible deficiencies in antigen presentation for ALL or potential effects of molecular mimicry in CML.

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Antecedentes: La presencia de HLA es un factor que influye en la patogénesis de las leucemias. Objetivos: Se evaluó la presencia de alelos HLA clase II DRB1*, DQB1*, DPA1* y DPB1* en 47 pacientes con leucemia linfoide aguda (LLA) y 48 con leucemia mieloide crónica (LMC), para compararlos con 48 voluntarios sanos de Zulia, Venezuela, y determinar las posibles asociaciones de HLA con las leucemias. Métodos: Se utilizó la técnica de PCR-SSP de baja y alta resolución para las regiones HLA clase II DRB1*, DQB1*, DPA1* y DPB1* conforme las instrucciones del KIT Olerup SSP Genovision. Resultados: Los alelos HLA-DRB1*14, especialmente DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, y los haplotipos HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 tuvieron asociación con LMC (RR > 3); los alelos HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 y los haplotipos HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 resultaron protectores (RR < 1). Los alelos HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 tuvieron asociación positiva con LLA. Los alelos HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 y los haplotipos HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 resultaron asociados negativamente. Conclusiones: La fuerte asociación de HLA DRB1*14 con la LMC y la ausencia de asociaciones DRB1* con LLA y los otros patrones de asociación identificados sugieren marcadas diferencias en las patogénesis de las leucemias, lo que orienta hacia posibles deficiencias en la presentación antigénica para LLA o posibles efectos de mimetismo molecular en LMC.

Assuntos

Antígenos HLA-D/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Alelos , Antígenos HLA-D/genética , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Haplótipos , Humanos , Venezuela

RESUMO

We analyzed 238 unrelated Mestizo (admixed) individuals from the West region of Mexico with the PowerPlex® Fusion System (Promega Corp.). Allele frequencies and forensic parameters were estimated for the 23 STRs included in this kit. Hardy-Weinberg equilibrium by locus and non-association between pair of loci were demonstrated by exact tests in this population. The combined PE and PD offered by this HID kit were ≥0.9999999986, representing a substantial improvement with respect to those previously offered by 15 STR systems. Interpopulation comparison by AMOVA tests demonstrated low but significant differences among Mexican Mestizos from West, Center, and Northeast regions (Fst = 0.01558; p = 0.0000), similar to the observed among three main ethnic groups from USA (Fst = 0.02048; p = 0.0000). This finding is consistent with the contrary clines of European and Amerindian ancestries described throughout the Mexican territory for Mestizos, the largest population (~90 %) in this country.

Assuntos

Etnicidade/genética , Genética Populacional , Repetições de Microssatélites , Impressões Digitais de DNA , Frequência do Gene , Humanos , México

RESUMO

Teeth proportions relate to beauty and harmony but aesthetic dental ideal proportion models show inconsistent results. Golden Proportion´s, Preston's, Fayyad's, Snow's, and Ward's models where characterized for best fit in a Colombian mestizo population anterior teeth. Models of teeth´s beauty proportions (Golden Proportion´s, Preston's, Fayyad's, Snow's, and Ward') are analyzed for best fit in a mestizo (mixed race) Colombian population and variables as sex, aesthetic balance or history of previous orthodontic treatments were also analyzed for their probable impact on the distribution of the dental proportions. It was used standardized photographs of anterior teeth on 351 individuals of both sexes with complete erupted and healthy teeth. The measurements were done by calibrated computer software (error of 0.05 mm). A Chi squared test was used to check whether sex, aesthetic balance and previous orthodontic treatment had an impact on the distribution of the dental proportions. Also a nonparametric Wilcoxon test was used to analysis the null hypothesis. A cluster analysis using k means was carried out to search for subgroups, which better explain the distribution of anterior dental proportions in the sample. For the considered results the null hypothesis of the mean equaling to the Golden Proportion was rejected (Wilcoxon test p value <0.001). For the whole population, the Chi squared test did not reject the null hypothesis of equal proportions among the groups with respect to the sex (p value= 0.56), aesthetic balance (p value= 0.98) and history of previous orthodontic treatments (p value= 0.67) variables. For the aesthetically balanced individuals, the Chi squared test also failed to reject the null hypothesis of equal proportions among the groups with respect to the sex (p value= 0.63) and history of previous orthodontic treatments (p value= 0.93) variables. Two Gaussian distributions were found for RED models fitting well in 58 % for RED 70 % (0.7 SD 0.03) and 42 % for RED 75 (0.75 SD 0.025). From the cluster analysis using k means, two groups were identified in the whole sample. No universal model can describe the whole population but is possible to find a set of models for the different population subgroups. Aesthetically ideals are open to interpretation. Clinical aesthetically standards for ideal teeth proportions are open to interpretation in a mestizo (mixed raced) population.

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Las proporciones de los dientes se refieren a su belleza y armonía, pero los modelos de proporciones dentales estéticas ideales muestran resultados inconsistentes. La proporción Aurea y los modelos de Preston, Fayyad, Snow, y Ward fueron ajustados para caracterizar los dientes de una población colombiana mestiza. Modelos de proporciones de belleza de dientes (Proporción Aurea, Modelos de Preston, Fayyad, Snow y Ward) se analizaron para lograr alcanzar el mejor ajuste en una población colombiana mestiza (mezcla de razas), y también se analizaron las variables de sexo, equilibrio estético e historia de tratamientos de ortodoncia previos para evaluar su probable impacto sobre la distribución de las proporciones dentales consideradas. Fueron utilizadas fotografías estandarizadas de dientes anteriores de 351 individuos de ambos sexos con dientes completamente erupcionados y sanos. Las mediciones fueron realizadas con programas informáticos calibrados (error de 0,05 mm). Se utilizó la prueba Chi Cuadrado para comprobar si el sexo, el equilibrio estético y el tratamiento ortodóncico previo tuvieron un impacto en la distribución de las proporciones dentales. También se utilizó la prueba no paramétrica de Wilcoxon para el análisis de la hipótesis nula. Un análisis de conglomerados, utilizando la media k, se llevó a cabo para buscar subgrupos, que explicaron mejor la distribución de proporciones dentales anteriores en la muestra. Para que los resultados fueran considerados, la hipótesis nula de la media que equivale a la proporción áurea fue rechazada (Prueba de Wilcoxon, valor p <0,001). Para toda la población, la prueba de Chi Cuadrado no rechazó la hipótesis nula de proporciones iguales entre los grupos con respecto al sexo (valor de p= 0,56), equilibrio estético (valor de p= 0,98) y la historia de tratamientos de ortodoncia previos ( valor de p= 0,67). Para los individuos estéticamente balanceados, la prueba de Chi Cuadrado tampocó rechazó la hipótesis nula de proporciones iguales entre los grupos con respecto a las variables de sexo (valor p= 0,63) y la historia de los tratamientos de ortodoncia anteriores (valor p= 0,93). Se encontraron dos distribuciones gaussianas para los modelos RED que encajaron bien en el 58% para RED 70 % (0,7 DE 0,03) y el 42 % para RED 75 (0,75 DE 0,025). Con respecto al análisis de los conglomerados a través de las medias k, se identificaron dos grupos en toda la muestra. No hay un modelo universal que pueda describir toda la población, pero es posible encontrar un conjunto de modelos para los diferentes subgrupos de población. Los ideales estéticamente están abiertos a interpretación. Las normas clínicas de estética para dientes con proporciones ideales están abiertos a interpretación en una población mestiza.

Assuntos

Humanos , Masculino , Feminino , Adolescente , Adulto , Etnicidade , Dente/anatomia & histologia , Colômbia

RESUMO

OBJECTIVE: The frequency of GJB2 mutations and of the del(GJB6-D13S1830) mutation has not been established among the Ecuadorian mestizo population diagnosed with autosomal recessive non-syndromic hearing loss. A genetic analysis was therefore designed in order to do so. METHODS: The sample population included 111 subjects of which 26 were autosomal recessive non-syndromic hearing loss probands. Posterior to PCR amplification, sequencing analysis of exon 2 was used for mutational detection of the GJB2 gene; a multiplex PCR method was used for detection of the del(GJB6-D13S1830) mutation. The ratio of subjects with a certain state of the mutation (heterozygous/homozygous) is expressed as a percentage and significant differences between probands and controls were calculated using Fisher's exact test; P<0.05 was considered significant. RESULTS: A total of 104 mutations belonging to 8 allelic variations were identified. The most common being the V27I (58.9%); however, as this variation is a non-pathogenic polymorphism, Q7X, with a total of 19 mutated alleles, was the most frequent mutation (18.3%). The V27I polymorphism was the only variation distributed homogenously among probands and controls (P=0.351). Based on physical analyses of multiple patients we confirm that Q7X causes a non-syndromic form of hearing loss and propose that it is a possible predominant mutation in the Ecuadorian population. CONCLUSIONS: This is the first study of its kind among the Ecuadorian population and a preliminary step in establishing GJB2 and del(GJB6-D13S1830) mutational frequencies in this population; it is also the first to report of such a high frequency of the Q7X mutation. The data presented here brings Ecuador a step closer to providing more efficient treatment for a broader number of patients; additionally, it contributes to a better understanding of the relationship between autosomal recessive non-syndromic hearing loss and mutations on the GJB2 gene.

Assuntos

Conexinas/genética , Perda Auditiva/genética , Mutação , Adolescente , Adulto , Idoso , Alelos , Conexina 26 , Equador , Éxons , Feminino , Testes Genéticos , Perda Auditiva/etnologia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Adulto Jovem

RESUMO

This study aims to portray the complex diversity of the Mexican Mestizo population, which represents 98.8% of the entire population of Mexico. We compiled extended haplotype data of the Y chromosome from populations in the Central Valley of Mexico (CVM), which we compared with other Mestizo and parental (Amerindian, European, and African) populations. A complex ancestral relationship was found in the CVM population, suggesting cosmopolitan origins. Nevertheless, the most preeminent lineages point toward a European ancestry, where the R1b lineage was most frequent. In addition, important frequencies of Amerindian lineages were also found in the Mestizo sample studied. Interestingly, the Amerindian ancestry showed a remarkable substructure, which was represented by the two main founding lineages: QL54 (× M3) and M3. However, even within each lineage a high diversity was found despite the small number of sample bearers of these lineages. Further, we detected important genetic differences between the CVM populations and the Mexican Mestizo populations from the north and south. This result points to the fact that Mestizo populations present different ancestral proportions, which are related to the demographic events that gave origin to each population. Finally, we provide additional forensic statistical parameters that are useful in the interpretation of genetic analysis where autosomal loci are limited. Our findings illustrate the complex genetic background of the Mexican Mestizo population and reinforce the need to encompass more geographic regions to generate more robust data for forensic applications.

Assuntos

Cromossomos Humanos Y/genética , Indígenas Norte-Americanos/genética , Filogenia , População Negra , Frequência do Gene , Variação Genética/genética , Genética Populacional , Haplótipos/genética , Humanos , México/epidemiologia , População Branca

RESUMO

PURPOSE: Obesity is a disease with genetic susceptibility characterized by an increase in storage and irregular distribution of body fat. In obese patients, the decrease in the Adiponectin gene (ADIPOQ) expression has been associated with a systemic low-grade inflammatory state. Our aim was to investigate the relationship between ADIPOQ +45T>G gene simple nucleotide polymorphism (SNP rs2241766) with serum adiponectin (sAdiponectin), distribution of body fat storage, and inflammation markers. SUBJECTS AND METHODS: In this cross-sectional study, 242 individuals from Western Mexico characterized as Mexican-Mestizo and classified by body mass index (BMI), were included. Anthropometrics, body composition, body fat distribution, and inflammation markers were measured by routine methods. Genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and sAdiponectin by the ELISA method. A P-value <0.05 was considered the statistically significant threshold. RESULTS: sAdiponectin is associated with BMI (P < 0.001) and the genotypes (P < 0.001 to 0.0046) GG (8169 ± 1162 ng/mL), TG (5189 ± 501 ng/mL), and TT (3741 ± 323 ng/mL), but the SNP ADIPOQ +45T>G is not associated with BMI. However, the detailed analysis showed association of this SNP with a pattern of fat distribution and correlations (P < 0.05) with inflammation markers and distribution of body fat storage (Pearson's r = -0.169 to -0.465) were found. CONCLUSION: In this study, we have suggested that the ADIPOQ +45G allele could be associated with distribution of body fat storage in obesity. On the other hand, as no association was observed between ADIPOQ +45T>G gene polymorphism and obesity, it cannot be concluded that the ADIPOQ +45G allele is responsible for the increase of adiponectin levels.