RESUMEN

The aim of this study was to evaluate whether polymorphisms in SOD2 and SOD3 genes modulate the oral health-related quality of life (OHRQoL) of Para athletes with dental caries experience. The cross-sectional study included 264 Para athletes (143 in athletics, 61 in weightlifting and 60 in swimming). A trained and calibrated team recorded the decayed, missing and filled teeth index (DMFT). The Brazilian version of the Oral Health Impact Profile (OHIP-14) was used to measure OHRQoL. Genomic DNA was extracted from the athletes' saliva, and genetic polymorphisms in the SOD2 (rs5746136 and rs10370) and SOD3 (rs2855262 and rs13306703) genes were analyzed by real-time polymerase chain reaction. Univariate and multivariate analyses were performed. A multivariate General Linear Model analysis, adjusted for sex, revealed that the SOD3 gene polymorphism (rs2855262) had a significant effect on the psychological disability domain [codominant (p = 0.045) and recessive (p=0.038) models]. The SOD2 gene polymorphism (rs5746136) had a significant effect on the total OHIP-14 score [dominant model (p = 0.038)] and the psychological discomfort [dominant model (p = 0.034)] and physical disability [codominant model (p=0.037)] domains. Presence of the SOD2 rs10370 polymorphism led to statistical differences in the total score [codominant (p = 0.026) and dominant (p = 0.023) models] and the handicap domain scores [codominant (p = 0.027) and dominant (p = 0.032) models]. Polymorphisms of the SOD2 and SOD3 genes may be important biomarkers of OHRQoL in Para athletes with dental caries experience.

Asunto(s)

Atletas , Salud Bucal , Calidad de Vida , Superóxido Dismutasa , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Análisis de Varianza , Atletas/psicología , Atletas/estadística & datos numéricos , Brasil , Estudios Transversales , Caries Dental/genética , Índice CPO , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Valores de Referencia , Saliva/química , Estadísticas no Paramétricas , Superóxido Dismutasa/genética

RESUMEN

The purpose of this study was to verify the association between angiotensin-converting enzyme (ACE) genotypes DD, DI, and II and caffeine (CAF) ingestion on endurance performance, heart rate, ratio of perceived exertion (RPE), and habitual caffeine intake (HCI) of adolescent athletes. Seventy-four male adolescent athletes (age: DD=16±1.7; DI=16±2.0; II=15±1.7 years) ingested CAF (6 mg/kg) or placebo (PLA) one hour before performing the Yo-Yo Intermittent Recovery level 1 (Yo-Yo IR1) test. No difference was found among groups for HCI. However, CAF increased the maximal distance covered and VO2max in DI and II genotype carriers compared to PLA (DD: Δ=31 m and 0.3 mL·kg-1·min-1; DI: Δ=286 m and 1.1 mL·kg-1·min-1; II: Δ=160 m and 1.4 mL·kg-1·min-1). Heart rate of DI and II genotype carriers increased with CAF compared to PLA, while RPE was higher in the II and lower in the DD genotypes. The correlations between HCI and maximal distance covered or VO2max were significant in the II genotype carriers with CAF. CAF increased endurance capacity, heart rate, and RPE in adolescent athletes with allele I, while endurance performance and aerobic power had a positive correlation to HCI in the II genotype group. These findings suggested that DD genotype were less responsive to CAF and that genetic variations should be taken into account when using CAF supplementation to enhance exercise performance.

Asunto(s)

Atletas , Cafeína , Genotipo , Frecuencia Cardíaca , Peptidil-Dipeptidasa A , Esfuerzo Físico , Humanos , Adolescente , Masculino , Frecuencia Cardíaca/efectos de los fármacos , Cafeína/administración & dosificación , Esfuerzo Físico/fisiología , Peptidil-Dipeptidasa A/genética , Rendimiento Atlético/fisiología , Resistencia Física/efectos de los fármacos , Resistencia Física/genética , Polimorfismo Genético/genética , Brasil , Consumo de Oxígeno/genética , Consumo de Oxígeno/efectos de los fármacos , Sustancias para Mejorar el Rendimiento/administración & dosificación

RESUMEN

This study aimed to assess the association between genetic polymorphisms in BMP2 (rs1005464 and rs235768), BMP4 (rs17563), SMAD6 (rs2119261 and rs3934908) and RUNX2 (rs59983488 and rs1200425) and pulp stones (PS). A total of 117 participants, consisting of 63 individuals with PS and 54 without PS, were included. Digital radiographs and a demographic/clinical questionnaire were used. Genomic DNA from salivary cells was genotyped via real-time polymerase chain reaction. Statistical analyses, including Chi-Square, Fisher's exact tests, Poisson regression and dimensionality reduction, were conducted. The rs2119261 polymorphism in the SMAD6 gene showed an association with genotype distribution in the recessive model (p = 0.049). The T-T haplotype in the SMAD6 gene (rs2119261 and rs3934908) was more prevalent in the control group and significantly linked with PS (p = 0.029). No associations were found between PS risk and genetic polymorphisms in BMP2, BMP4 and RUNX2. Polymorphisms in the SMAD6 gene were associated with PS.

Asunto(s)

Proteína Morfogenética Ósea 2 , Proteína Morfogenética Ósea 4 , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Proteína smad6 , Humanos , Proteína smad6/genética , Proteína Morfogenética Ósea 4/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Masculino , Femenino , Proteína Morfogenética Ósea 2/genética , Adulto , Polimorfismo de Nucleótido Simple , Genotipo , Polimorfismo Genético/genética , Adulto Joven , Estudios de Casos y Controles

RESUMEN

BACKGROUND: Molar hypomineralization (MH) is defined as a multifactorial condition, and thus, its presence may be defined by interactions between environmental and genetic factors. AIM: To evaluate the association between MH, genes involved in enamel development, and the use of medication during pregnancy in early childhood. DESIGN: One hundred and eighteen children, 54 with and 64 without MH, were studied. The data collected included demographics, socioeconomic data, and the medical history of mothers and children. Genomic DNA was collected from saliva. Genetic polymorphisms in ameloblastin (AMBN; rs4694075), enamelin (ENAM; rs3796704, rs7664896), and kallikrein (KLK4; rs2235091) were evaluated. These genes were analyzed by real-time polymerase chain reaction using TaqMan chemistry. The software PLINK was used to compare allele and genotype distributions of the groups and to assess the interaction between environmental variables and genotypes (p < .05). RESULTS: The variant allele KLK4 rs2235091 was associated with MH in some children (odds ratio [OR]: 3.75; 95% confidence interval [CI] = 1.65-7.81; p = .001). Taking medications in the first 4 years of life was also associated with MH (OR: 2.94; 95% CI = 1.02-6.04; p = .041) and specifically in association with polymorphisms in ENAM, AMBN, and KLK4 (p < .05). The use of medications during pregnancy was not associated with MH (OR: 1.37; 95% CI = 0.593-3.18; p = .458). CONCLUSION: The results of this study suggest that taking medication in the postnatal period appears to contribute to the etiology of MH in some evaluated children. There may be a possible genetic influence of polymorphisms in the KLK4 gene with this condition.

Asunto(s)

Hipomineralización Molar , Niño , Femenino , Humanos , Preescolar , Amelogénesis/genética , Genotipo , Polimorfismo Genético/genética , Esmalte Dental

RESUMEN

One of the main challenges in the clinical management of dengue is the early identification of cases that could progress to severe forms of the disease. A biomarker that may enable this identification is the presence of genetic polymorphisms in genes associated with immune responses. The objective of this study was to perform a systematic review of the Latin American literature on these genes. An electronic literature search was carried out in PubMed, Scopus, Lilacs, and the Virtual Health Library, and reference lists of systematic reviews in the area. Case-control studies conducted in Latin American countries examining at least one form of genetic polymorphism related to immune responses against severe dengue were included. In total, 424 articles were identified and 26 were included in this systematic review. Of the 26 selected articles, 16 reported polymorphisms associated with the risk of developing severe dengue (Risk); Similarly, 16 articles reported polymorphisms associated with a decreased risk of severe dengue (Protective). The final analysis revealed that multiple polymorphisms in immune system genes were early markers of the progression of dengue in Latin Americans and found that polymorphisms of the TNF-alpha gene may have a critical role in dengue pathogenesis.

Asunto(s)

Dengue , Dengue Grave , Humanos , Dengue Grave/genética , América Latina , Dengue/genética , Revisiones Sistemáticas como Asunto , Polimorfismo Genético/genética

RESUMEN

Passiflora edulis it is a specie widely distributed and cultivated in Colombia, with economic potential. Although there is a wide genetic and phenotypic variability, it has not yet been explored through the use of molecular techniques. This study aimed to characterize the structure and genetic diversity of P. edulis cultivars using ISSR markers. The study was carried out using leaf samples from 21 cultivars of P. edulis collected within a productive system in the department of Boyacá, Colombia, using seven ISSR primers. Genetic similarity was used to cluster by the UPGMA method, polymorphic information content (PIC), expected heterozygosity (He), Shannon index (I), gene flow (Nm), and coefficient of genetic differentiation (Gst) were estimated using POPGENE and TFPGA software. The Bayesian model and analysis of molecular variance (AMOVA) were used to assess the genetic structure. Cultivars of P. edulis showed high polymorphism rates. Seven ISSR produced 138 loci. The cluster analysis formed two groups according to the genetic similarity and phenotypic characteristics associated mainly with the fruit. The average value of expected heterozygosity was 0.29 for the total population and 0.27 and 0.22 for groups I and II, respectively. AMOVA indicates higher diversity within groups, but not between groups showing levels of hierarchy different from those considered in this study. Moderate genetic differentiation (Gst=0.12) and high gene flow (Nm=3.91) are observed.

Asunto(s)

Passiflora , Passiflora/genética , Teorema de Bayes , Polimorfismo Genético/genética , Análisis por Conglomerados , Frutas

RESUMEN

Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases.

Asunto(s)

Diabetes Mellitus , Hipertensión , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Actinina/genética , Arildialquilfosfatasa/genética , Glucemia , Colesterol , Diabetes Mellitus/genética , Genotipo , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Triglicéridos

RESUMEN

Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (-202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Asunto(s)

Enfermedad del Hígado Graso no Alcohólico , Humanos , Estudios de Asociación Genética , Genotipo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Polimorfismo Genético/genética

RESUMEN

BACKGROUND: A 100-bp insertion/deletion polymorphism in the pepsinogen C gene has been associated with the risk of gastric cancer (GC). OBJECTIVE: We analyzed the relationships of the 100-bp insertion/deletion polymorphism with GC, atrophic gastritis (AG), and intestinal metaplasia (IM) in the Mexican general population (MGP). METHODS: We studied the genomic DNA of subjects with GC n = 80, AG and IM n = 60, controls n = 110, and the MGP n = 97. PGC gene insertion/deletion polymorphism was identified by means of PCR, capillary electrophoresis and GeneScan software. RESULTS: Different allele sizes of PGC polymorphism were observed in the studied groups, from 266 bp to 499 bp, which were grouped for the analysis as short alleles of 266-399 bp, medium alleles of 400-433 bp and large alleles of 434-499 bp. Carriers of one or two medium alleles, had an increased risk of GC, with OR of 1.99 (CI95% 1.08-3.67 p = 0.026) compared to homozygotes (no medium/no medium). CONCLUSIONS: Previous studies have related PGC short alleles to risk for or protection against GC depending on the ethnic origin of the population. In our study, medium alleles were related to risk for GC. Further studies are required to establish the importance of this polymorphism in the origin of gastric neoplasia.

Asunto(s)

Gastritis Atrófica , Pepsinógeno C , Neoplasias Gástricas , Humanos , Alelos , Gastritis Atrófica/genética , Gastritis Atrófica/complicaciones , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Polimorfismo Genético/genética , Factores de Riesgo , Neoplasias Gástricas/genética , Pepsinógeno C/genética

RESUMEN

BACKGROUND: The variability in tooth crown size (TCS) is influenced by genetic factors and might be regulated by the difference in hormonal response. MATERIALS AND METHODS: This study aimed to evaluate the association between variations in TCS of permanent teeth with associated factors and genetic polymorphisms in hormonal-related genes (ESR1, ESR2 and PTH). This cross-sectional study involved dental casts from 86 individuals of both sexes. Dental casts were used to determine the maximum TCS of all fully erupted permanent teeth (except third molars) in the mesiodistal (MD) and buccolingual (BL) dimensions. Data such as sex, ethnicity, dental group (incisor, canine, premolar and molar), dental arch (upper and lower) and genetic polymorphisms of hormonal-related genes were used. The DNA from each patient was collected to evaluate the genetic polymorphisms in ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938) and PTH (rs694, rs6256 and rs307247) through real-time PCR. The data were submitted to statistical analysis with a significance level of 0.05. RESULTS: In the MD dimension, the sex, dental group and dental arch were associated with variation in TCS (P < .05). In the BL dimension, the sex, dental group, dental arch and polymorphism in rs694 and rs307247 were associated with variation in TCS. CONCLUSIONS: In short, this study suggests that genetic polymorphisms of PTH are associated with variations in the BL TCS of permanent human teeth.

Asunto(s)

Corona del Diente , Diente , Masculino , Femenino , Humanos , Estudios Transversales , Dentición Permanente , Diente Premolar , Polimorfismo Genético/genética , Odontometría/métodos

RESUMEN

BACKGROUND: The semi-domesticated Brazilian perennial cotton (Gossypium spp.) germplasm is considered a source of variability for creating modern upland cotton varieties. Here we used Inter-simple Sequence Repeat (ISSR) markers to detect intra and interspecific genetic polymorphism in Gossypium hirsutum L. r. marie-galante and Gossypium barbadense L. and to use molecular data to assessing genetic diversity and molecular discrimination of these species. METHODS AND RESULTS: The sets contained 12 G. barbadense genotypes and 16 G. hirsutum genotypes from a Brazilian collection. The 11 ISSR primers were used for genotyping yielded 101 bands (polymorphism = 47.5%) and were classified as moderately informative (PIC = 0.304). The ISSR markers exposed a greater diversity in G. hirsutum (P = 24.72%; HE =0.071 and I = 0.111) as compared to G. barbadense (P = 17.98%, HE = 0.043 and I = 0.070). The AMOVA analysis showed that 89.47% of the genetic variation was partitioned within species which is supported by Nei's genetic differentiation (Gst = 0.598) and gene flow (Nm = 0.338), suggesting that strong reproductive barriers between species. The UPGMA Cluster Analysis, Principal Coordinate Analysis and Bayesian Model-Based Structural Analysis divided the 28 genotypes into two main clades consistent with the taxonomical delimitation. CONCLUSION: The ISSR marker system offers a new approach to determining molecular differences between two cotton species (G. hirsutum L. r. marie-galante and G. barbadense L.). This study can expand the molecular marker resources for the identification and improvement of our knowledge about the genetic diversity and relationships between perennial cotton genotypes.

Asunto(s)

Gossypium , Polimorfismo Genético , Gossypium/genética , Teorema de Bayes , Brasil , Polimorfismo Genético/genética , Repeticiones de Microsatélite/genética , Variación Genética/genética

RESUMEN

BACKGROUND: Abnormalities in the different stages of the intestinal maturation process cause metabolic and molecular changes. Among the genetic alterations associated with necrotizing enterocolitis, the -94ins/delATTG polymorphism in NFKB1 gene leads to unregulated activation of the NFKB protein due to an increase in the inherent pro-inflammatory state of the premature intestine. AIMS: To determine the prevalence of the -94ins/delATTG polymorphism in NFKB1 gene in neonates with and without necrotizing enterocolitis. METHODS: This is a case-control study, in which 25 neonates were evaluated as the case group and 50 neonates as the control group, of both genders. DNA was extracted from peripheral blood leukocytes, and the site encompassing the polymorphism was amplified by molecular techniques (polymerase chain reaction/polymorphism in restriction fragment length). RESULTS: Necrotizing enterocolitis was diagnosed in 25 (33%) neonates and, of these, 3 (12%) died. Male gender was more prevalent in both groups (p=0.1613): cases (52%) and controls (62%). Moderate and extreme preterm newborns were predominant in both groups: cases (80%) and controls (88%) (p=0.3036). Low birth weight and extremely low birth weight newborns were the most prevalent in cases (78%), and very low birth weight and extremely low birth weight were the most prevalent in controls (81%) (p=0.1073). Clinical treatment was successful in 72%, and hospital discharge was achieved in 88% of newborns with NEC. The -94ins/delATTG polymorphism in NFKB1 gene was not identified in all the 150 alleles analyzed (100%). CONCLUSIONS: The absence of the -94ins/delATTG polymorphism in NFKB1 gene in newborns with and without necrotizing enterocolitis does not rule out the possibility of alterations in this and/or in other genes in newborns with this condition, which reinforces the need for further research.

Asunto(s)

Enterocolitis Necrotizante , Neoplasias del Recto , Masculino , Humanos , Recién Nacido , Femenino , Estudios de Casos y Controles , Enterocolitis Necrotizante/genética , Subunidad p50 de NF-kappa B/genética , Polimorfismo Genético/genética , Mutación

RESUMEN

Breast cancer was declared the most prevalent type of cancer in 2020. Among other factors, treatment response can be affected by genetic polymorphisms - which is the focus of pharmacogenetics - and ethnicity is also a contributing factor in this context. Relevant genes in disease treatment pathways were selected to evaluate treatment response from the pharmacogenetic perspective; polymorphism frequencies and ethnic and continental representation across the available literature were also assessed through a systematic review. The identified associations and gaps have been described in this study with the purpose that, in the future, treatments can be personalized and thus be more effective, safer, and accessible to all.

Asunto(s)

Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Polimorfismo Genético/genética , Farmacogenética , Etnicidad

RESUMEN

The aim of this study was to analyze the association between ACE (DD + ID versus II) and ACTN3 (TT + TC versus CC) polymorphisms in the response of multicomponent physical training programs and combined in the health parameters of physically active women aged 50 to 75 years. Participants were randomly divided into two groups: multi-component training and combined training. Intervention lasted 14 weeks, 180 minutes a week. Genomic DNA was extracted from blood samples and genotyping analyzes were performed by conventional and real-time PCR. Associations were observed between polymorphisms in anthropometric measurements, blood pressure, physical capacity and quality of life in both models physical training, with improvement in group II - (ACE- multicomponent training in terms of abdominal circumference and sit-to - Combined training in terms of waist circumference) and TT + TC group (ACTN3 - multicomponent training in tests of muscle strength and mental quality of life domain, and combined training in body mass index, waist circumference, diastolic blood pressure, upper limb strength and cardiorespiratory capacity). Fourteen weeks of multicomponent and combined physical training in physically active women aged 50 to 75 years resulted in greater health benefits for genotypes II (ACE) and TT + TC (ACTN3).

Asunto(s)

Actinina , Peptidil-Dipeptidasa A , Actinina/genética , Anciano , ADN , Ejercicio Físico , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Calidad de Vida

RESUMEN

BACKGROUND: The enzyme methylenetetrahydrofolate reductase is engaged in DNA synthesis through folate metabolism. Inhibiting the activity of this enzyme increases the susceptibility to mutations, and damage and aberrant DNA methylation, which alters the gene expression of tumor suppressors and proto-oncogenes, potential risk factors for esophageal cancer. AIMS: This study aimed to investigate the association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and susceptibility to esophageal cancer, by assessing the distribution of genotypes and haplotypes between cases and controls, as well as to investigate the association of polymorphisms with clinical and epidemiological characteristics and survival. METHODS: A total of 109 esophageal cancer patients who underwent esophagectomy were evaluated, while 102 subjects constitute the control group. Genomic DNA was isolated from the peripheral blood buffy coat followed by amplification by polymerase chain reaction and real-time analysis. Logistic regression was used to assess associations between polymorphisms and the risk of developing esophageal cancer. RESULTS: There was no association for methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and haplotypes, with esophageal cancer susceptibility. Esophageal cancer patients carrying methylenetetrahydrofolate reductase 677TT polymorphism had higher risk of death from the disease. For polymorphic homozygote TT genotype, the risk of death significantly increased compared to wild-type genotype methylenetetrahydrofolate reductase 677CC (reference) cases (p=0.045; RR=2.22, 95%CI 1.02-4.83). CONCLUSIONS: There was no association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and esophageal cancer susceptibility risk. Polymorphic homozygote genotype methylenetetrahydrofolate reductase 677TT was associated with higher risk of death after surgical treatment for esophageal cancer.

Asunto(s)

Neoplasias Esofágicas , Metilenotetrahidrofolato Reductasa (NADPH2) , Estudios de Casos y Controles , ADN , Neoplasias Esofágicas/genética , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Oxidorreductasas/genética , Polimorfismo Genético/genética

RESUMEN

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.

Asunto(s)

Dengue , Virosis , Teorema de Bayes , Dengue/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Metaanálisis como Asunto , Polimorfismo Genético/genética

RESUMEN

Recent studies have shown that two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

Asunto(s)

Hipotiroidismo , Metilenotetrahidrofolato Reductasa (NADPH2) , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Humanos , Hipotiroidismo/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo

RESUMEN

Efavirenz (EFV) is a widely used antiretroviral, due to its safety, efficacy, and low cost. However, plasma concentrations have been related with an increased risk of virological failure and the appearance of serious adverse reactions. EFV is metabolized by Cytochrome P450, the main isoenzyme involved is CYP2B6 and the most relevant genetic polymorphisms found in several populations has been the CYP2B6 516G> T. The aim of this study was to identify the frequency of the CYP2B6 516G>T polymorphism and its effect on the plasma concentration of efavirenz (EFV) in a group of people living with HIV (PLWH) and undergoing EFV treatment in Morelos, Mexico. Ninety-six PLWH undergoing EFV treatment, at a daily dose of 600 mg orally in combination with other antiretrovirals (ARVs), were included in this study. The CYP2B6 516G>T polymorphism was detected using PCR-RFLP. The plasma concentrations of EFV were evaluated by high-resolution liquid chromatography coupled to a mass-mass detector, using a protein precipitation method. The median plasma EFV concentration was 4.6 µg/mL (IQR = 4.64) and 64.6% of the subjects had concentrations above the therapeutic range. The CYP2B6 516G>T genotype findings were as follows: 46.9% of the population presented the wild-type genotype (GG), while 45.8 % and 7.3 % showed the heterozygote (GT) and the polymorphic homozygote (TT) genotype, respectively. The homozygote G had the lowest plasma concentrations of EFV (median = 4.1 µg/mL and IQR = 1.7 µg/mL), followed by those with the GT genotype (median = 5.1 µg/mL and IQR = 3.0 µg/mL). Participants with the homozygous T genotype had the highest EFV concentrations (median = 9.7 µg/mL and IQR = 5.8 µg/mL). In conclusion, the CYP2B6 516G>T polymorphism was associated with plasma levels of EFV in PLWH undergoing ARV treatment. EFV plasma concentrations at 600mg doses were outside the therapeutic range in most subjects.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas , Ciclopropanos , Citocromo P-450 CYP2B6/genética , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/genética , Humanos , México , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple/genética

RESUMEN

BACKGROUND: Important risk factors for the most common sexually transmitted infection (STI) in the world, human papillomavirus (HPV), include early sexual activity, use of contraceptives, tobacco smoking, and immunological and genetic factors. This study aimed to investigate the relationship between GSTM1 and GSTT1 polymorphisms and HPV infection and associated risk factors in a group of women assisted in the public health system of southwestern Paraná, Brazil. METHODS AND RESULTS: A case-control study was designed with 21 women with HPV matched by age in the case group and 84 women without the virus in the control group. Viral detection was conducted via polymerase chain reaction (PCR) and GSTM1 and GSTT1 genotyping by Multiplex PCR. The results showed that the GSTT1 null allele was a protective factor against infection (ORadj 0.219; 95% CI 0.078-0.618; p = 0.004). No relationship was observed for the GSTM1 gene. Smoking was defined as a risk factor (ORadj 3.678; 95% CI 1.111-12.171; p = 0.033), increasing the chances of HPV by up to 3.6 times. CONCLUSION: This study showed, for the first time, the relationship between GSTM1 and GSTT1 genetic polymorphisms and HPV. We found that this relationship protected women from southern Brazil from viral infection, but not from susceptibility.

Asunto(s)

Glutatión Transferasa/genética , Infecciones por Papillomavirus , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genética , Polimorfismo Genético/genética , Factores de Riesgo

Asunto(s)

Labio Leporino , Fisura del Paladar , Estudios de Casos y Controles , Labio Leporino/genética , Fisura del Paladar/genética , Predisposición Genética a la Enfermedad , Genotipo , Proteínas de Homeodominio/genética , Humanos , Polimorfismo Genético/genética , Factores de Transcripción/genética