RESUMO
OBJECTIVE: We analyzed baseline and follow-up characteristics related to poorer renal outcomes in a Brazilian cohort of admixture race patients with lupus nephritis. METHODS: Overall, 280 outpatients with a diagnosis of systemic lupus erythematosus and previous kidney biopsy of lupus nephritis were recruited from August 2015 to December 2018 and had baseline laboratory and histologic data retrospectively analyzed; patients were then followed-up and data were recorded. The main outcome measure was the estimated glomerular filtration rate at last follow-up. Secondary analyses assessed the impact of initial kidney histology and treatment in long-term kidney survival. RESULTS: Median duration of lupus nephritis was 60 months (interquartile range: 27-120); 40 (14.3%) patients presented progressive chronic kidney disease (estimated glomerular filtration rate <30 and ≥10 ml/min/1.73 m2) or end-stage kidney disease at last visit. Adjusted logistic regression analysis showed that class IV lupus nephritis (odds ratio 14.91; 95% confidence interval 1.77-125.99; p = 0.01) and interstitial fibrosis ≥25% at initial biopsy (odds ratio 5.87; 95% confidence interval 1.32-26.16; p = 0.02), lack of complete or partial response at 12 months (odds ratio 16.3; 95% confidence interval 3.74-71.43; p < 0.001), and a second renal flare (odds ratio 4.49; 95% confidence interval 1.10-18.44; p = 0.04) were predictors of progressive chronic kidney disease. In a Kaplan-Meier survival curve we found that class IV lupus nephritis and interstitial fibrosis ≥25% were significantly associated with end-stage kidney disease throughout follow-up (hazard ratio 2.96; 95% confidence interval 1.3-7.0; p = 0.036 and hazard ratio 4.96; 95% confidence interval 1.9-12.9; p < 0.0001, respectively). CONCLUSION: In this large cohort of admixture race patients, class IV lupus nephritis and chronic interstitial damage at initial renal biopsy together with non-response after 1 year of therapy and relapse were associated with worse long-term renal outcomes.
Assuntos
Progressão da Doença , Falência Renal Crônica/etiologia , Nefrite Lúpica/fisiopatologia , Adulto , Brasil , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Nefrite Lúpica/classificação , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
Preterm birth (PTB) is featured by less than 37weeks of gestational age or fewer than 259days since the first day from the last menstrual period. Complications of PTB are the major cause of neonatal deaths, several factors are linked to PTB increased risk including immunological and genetics. Vitamin D plays an important role in immune response modulation and its action occurs through the vitamin D receptor (VDR), which recently has been described as overexpressed in human placenta during the pregnancy. Herein we assessed two single nucleotide polymorphisms (SNPs) FokI (rs2228570 A>G) and Cdx-2 (rs11568820 T>C), within VDR, using TaqMan fluorogenic probes, and differential susceptibility to SPTB. We assessed 104 pregnant women with SPTB and 85 women with normal birth in a Northeastern Brazilian population. Statistically significant differences for both SNPs where found when comparing allele and genotype frequencies in both groups: the T allele for rs2228570 and A allele for rs11568820 were significantly more frequent in SPTB group than in normal birth group (p=0.000013 and p=0.00466, respectively). The rs11568820 A/A genotype was associated to clinical/demographic variables such as: premature birth (p=0.007), neonate weight (p=0.039), presence of infection during pregnancy (p=0.011) and premature birth among multiparous (p=0.015). The rs2228570 T/T genotype associated with gestational diabetes mellitus (p=0.044) and chorioamnionitis during pregnancy (p=0.043). In conclusion our findings indicate an association between polymorphisms FokI and Cdx-2 within VDR gene and SPTB, suggesting their involvement in the triggering of these syndromes.
Assuntos
Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/genética , Receptores de Calcitriol/genética , Brasil , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Gravidez , Fatores de RiscoRESUMO
Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.
Assuntos
Anticoncepcionais Orais/efeitos adversos , Glutationa S-Transferase pi/genética , Infecções por Papillomavirus/epidemiologia , Polimorfismo de Nucleotídeo Único , Lesões Intraepiteliais Escamosas Cervicais/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Lesões Intraepiteliais Escamosas Cervicais/epidemiologiaRESUMO
The use of Y chromosome haplotypes, important for the detection of sexual crimes in forensics, has gained prominence with the use of databases that incorporate these genetic profiles in their system. Here, we optimized and validated an amplification protocol for Y chromosome profile retrieval in reference samples using lesser materials than those in commercial kits. FTA® cards (Flinders Technology Associates) were used to support the oral cells of male individuals, which were amplified directly using the SwabSolution reagent (Promega). First, we optimized and validated the process to define the volume and cycling conditions. Three reference samples and nineteen 1.2 mm-diameter perforated discs were used per sample. Amplification of one or two discs (samples) with the PowerPlex® Y23 kit (Promega) was performed using 25, 26, and 27 thermal cycles. Twenty percent, 32%, and 100% reagent volumes, one disc, and 26 cycles were used for the control per sample. Thereafter, all samples (N = 270) were amplified using 27 cycles, one disc, and 32% reagents (optimized conditions). Data was analyzed using a study of equilibrium values between fluorophore colors. In the samples analyzed with 20% volume, an imbalance was observed in peak heights, both inside and in-between each dye. In samples amplified with 32% reagents, the values obtained for the intra-color and inter-color standard balance calculations for verification of the quality of the analyzed peaks were similar to those of samples amplified with 100% of the recommended volume. The quality of the profiles obtained with 32% reagents was suitable for insertion into databases.
Assuntos
Cromossomos Humanos Y/genética , Genética Forense/métodos , Haplótipos , Reação em Cadeia da Polimerase/métodos , Bases de Dados de Ácidos Nucleicos , Humanos , Masculino , Repetições de MicrossatélitesRESUMO
Osteoporosis is a multifactorial and debilitating disease resulting from decreased bone mineral density (BMD) and loss of tissue microarchitecture. Ineffective therapies may lead to bone fractures and subsequent death. Single nucleotide polymorphisms (SNPs) in key immune regulator genes have been associated with therapeutic response to bisphosphonates, which are the first therapeutic line of choice for osteoporosis. However, cytokine pathways and their relation with therapeutic adhesion remain to be fully elucidated. Aimed at better understanding these processes, we investigated the response to bisphosphonate therapy in postmenopausal women and four SNPs in key proinflammatory cytokines genes: IL23R +2284 (C>A) (rs10889677), IL17A +672 (G>A) (rs7747909), IL12B +1188 (T>G) (rs3212227) and INF-γ -1616 (G>A) (rs2069705). A total of 69 patients treated with bisphosphonate were followed for a period of 1 up to 4 years, genotyped and compared according to their changes in bone mineral density (BMD) and level of biochemical markers during their treatment. The INF-γ -1616 G/G associated with increased BMD values in femoral neck (GG/AA, p = 0.016) and decreased BMD values in total hip (GG/GA, p = 0.019; GG/AA, p = 0.011). In relation to biochemical markers, INF-γ -1616 SNP associated with increased alkaline phosphatase (GG/AA; p < 0.0001) and parathyroid hormone levels (AA/GA; p = 0.017). Vitamin D values changes were related to IL17A +672 (GG/GA, p = 0.034) and to IL12B +1188 (TT/TG, p = 0.046) SNPs. Besides, significant differences in changes of calcium levels correlated with IL23R +2284 (CC/CA, p = 0.016) genotypes. Altogether, we suggest that these polymorphisms may play an important role for therapeutic decisions in osteoporosis treatment.
Assuntos
Densidade Óssea/genética , Citocinas/genética , Difosfonatos/farmacologia , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único/genética , Pós-Menopausa/genética , Idoso , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/genética , Citocinas/metabolismo , Difosfonatos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismoRESUMO
Zidovudine, the antiretroviral drug used to treat HIV infection, commonly causes adverse effects, such as systemic fever and gastrointestinal alterations. In the present study, the potential role of inosine triphosphate pyrophosphatase (ITPA) gene variant on the incidence of adverse events during antiretroviral therapy (ART) of HIV with zidovudine was discussed. Individuals from Northeastern Brazil (N = 204) receiving treatment for HIV-1 infection were recruited. Zidovudine-related adverse effects developed during the treatment were registered. The rs1127354 polymorphism in the ITPA gene was genotyped using real-time PCR to assess whether this single nucleotide polymorphism was associated with the occurrence of zidovudine-related adverse effects. We observed a significant association between the ITPA variant genotype and the reported systemic fever (odds ratio = 7.17, 95% confidence interval = 1.19-43.15; P = 0.032). Zidovudine use could indirectly lead to an increase in the levels of inosine monophosphate in an antimetabolite-like manner, which is converted to inosine triphosphate (ITP). The rs1127354 variant caused a decrease in ITPA activity, thereby leading to ITP accumulation. This in turn resulted in cytotoxicity, which was manifested by neutropenia and fever. Therefore, we hypothesized a pharmacogenetic model involving the ITPA variant genotype in multifactorial components that act together to determine the onset of zidovudine-related adverse effects.
Assuntos
Antivirais/efeitos adversos , Febre/epidemiologia , Febre/etiologia , Infecções por HIV/complicações , Infecções por HIV/genética , Pirofosfatases/genética , Zidovudina/efeitos adversos , Antivirais/uso terapêutico , Brasil , Genótipo , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Zidovudina/uso terapêuticoAssuntos
Artrite Reumatoide , Proteínas de Transporte de Cátions/genética , Zinco , Adulto , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Brasil , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , Zinco/metabolismo , Zinco/farmacologiaRESUMO
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder presenting heterogeneous clinical manifestations. A number of genes involved in SLE susceptibility are related to the type I interferon (IFN) pathway. IFN mediates innate immune responses and its increased levels contribute to the breakdown of peripheral tolerance. Interferon-induced helicase C domain 1 (IFIH1) activates and modulates IFN responses through its caspase recruitment domain. In this study, we analyzed four IFIH1 single nucleotide polymorphisms (SNPs): rs6432714, rs10930046, rs1990760, and rs3747517, in 337 patients with SLE and 373 healthy individuals from southeast and northeast Brazil. Our results did not find an association between IFIH1 SNPs and SLE (P value >0.025 after Bonferroni's adjustment). However, meta-analysis of peer-reviewed articles from 2008 to 2015 and data from this study indicated an association between rs1990760 and SLE onset (P < 0.05). This is the first association analysis on IFIH1 polymorphisms and SLE susceptibility in Brazilian populations.
Assuntos
Estudos de Associação Genética , Interferon Tipo I/genética , Helicase IFIH1 Induzida por Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Brasil , Predisposição Genética para Doença , Humanos , Imunidade Inata/genética , Lúpus Eritematoso Sistêmico/patologia , Polimorfismo de Nucleotídeo Único , Transdução de SinaisRESUMO
The use of insects to answer questions in criminal investigations, as well as a combination of forensic genetic techniques to obtain human DNA from the organisms, especially necrophagous dipterians, have gained ground in recent decades among researchers and professionals in this area. The objective of our study was to evaluate and compare two methods of human DNA extraction, commonly used for forensic samples, to obtain human autosomal DNA and X chromosome short tandem repeat profiles from the digestive tract of Chrysomya albiceps (Diptera: Calliphoridae) larvae. Immature specimens were collected from corpses at the Institute of Forensic Medicine of Pernambuco and raised in bovine ground meat to allow stabilization of the colony. Groups of larvae in the third instar were provided with bovine ground meat plus human blood for 48 h, dissected, and then subjected to DNA extraction. DNA was extracted using two methods: a DNA IQ™ kit and a phenol-chloroform method. Genomic DNA was amplified using AmpFâSTR® Identifiler® Plus PCR and Argus-X-12® kits, and samples were sequenced to determine if the two extraction techniques generated reliable profiles that were compatible with a reference sample. The existence of comparable profiles from both techniques demonstrates the usefulness of dipteran larvae for obtaining human DNA from corpses, which can be further used to correlate genetic profiles in a crime scene when other traces are not available. However, several variables still require revision; thus, the technique should be further investigated for its validity, security, and, in particular, its reproducibility.
Assuntos
Cromossomos Humanos X/genética , DNA/genética , Dípteros/genética , Repetições de Microssatélites/genética , Animais , DNA/isolamento & purificação , Sistema Digestório/metabolismo , Loci Gênicos , Haplótipos/genética , Humanos , Larva , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals.
Assuntos
Aedes/química , Impressões Digitais de DNA/métodos , DNA/isolamento & purificação , Genética Forense/métodos , Aedes/fisiologia , Animais , Mordeduras e Picadas/sangue , Células Sanguíneas/química , Crime , DNA/genética , Feminino , Testes Genéticos/métodos , Voluntários Saudáveis , Humanos , Masculino , Repetições de MicrossatélitesRESUMO
Human leukocyte antigen (HLA)-G is a key tolerogenic molecule mainly expressed in the placenta and is crucial for implantation of the embryo and immunological tolerance of the fetus during pregnancy. However, under pathological conditions, such as cancer or viral infections, HLA-G can be expressed in other tissues. The gene coding for HLA-G (HLA-G, chromosome 6p21.3) presents numerous polymorphisms, some of them influencing its expression. One of the most studied, is the 14 bp ins/del (rs371194629) situated at the 3'-UTR of the gene. The insertion is thought to stabilize HLA-G mRNA. Different studies have analyzed the role of rs371194629 in hepatic injury, with either hepatotropic virus infection (i.e., HBV or HCV) or hepatocellular carcinoma (also induced by viral infection). Results from these studies are heterogeneous, differing with ethnicity and population age, and the role of rs371194629 is unclear. For these reasons, we decided to perform a meta-analysis of these results, concluding that the 14-bp ins/del polymorphism does not significantly contribute to hepatic injury.
Assuntos
Carcinoma Hepatocelular/genética , Antígenos HLA-G/genética , Mutação INDEL , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiões 3' não Traduzidas , Adulto , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Expressão Gênica , Frequência do Gene , Genótipo , Antígenos HLA-G/imunologia , Humanos , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
PROBLEM: Only a small proportion of HPV+ women develop virus-associated lesions and cervical cancer, suggesting that other factors are involved in HPV+ keratinocyte transformation. Immune response plays an important role in clearing HPV infection, and host genetic variants resulting in defective immune response have been associated with virus persistence and/or cervical cancer. Considering that genetic variations in inflammasome genes were previously associated with viral infection and cancer development, the present study investigates selected single nucleotide polymorphisms (SNPs) in inflammasome genes as a possible risk factor for HPV infection susceptibility and/or for progression to cervical cancer. PATIENTS AND METHODS: 12 SNPs in seven inflammasome-related genes (NLRP1, NLRP3, NLRP6, CARD8, IL1B, IL18, TNFAIP3) were genotyped in a Brazilian HPV+ case/control cohort (n = 246/310). Multivariate analysis was performed in case/control as well as in HPV+ women stratified by the presence or severity of histologic lesion, HPV persistence, and type of virus. RESULTS: IL1B rs1143643 was associated with protection against HPV infection in case/control analysis. NLRP1 rs11651270 plays a protection role against HPV persistence and/or oncogenesis. NLRP3 rs10754558 and IL18 rs1834481 exert a beneficial role against HPV persistence. NLRP3 rs10754558 variant resulted significantly associated with a lower risk to be infected with a high-risk HPV. CONCLUSION: Our findings for the first time demonstrated that inflammasome genetics could affect HPV/host interaction in terms of virus susceptibility as well as of virus/persistence and cervical cancer progression. J. Med. Virol. 88:1646-1651, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Predisposição Genética para Doença , Inflamassomos/genética , Infecções por Papillomavirus/imunologia , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/virologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Proteínas Reguladoras de Apoptose/genética , Brasil/epidemiologia , Proteínas Adaptadoras de Sinalização CARD/genética , Progressão da Doença , Feminino , Genótipo , Interações Hospedeiro-Patógeno , Humanos , Inflamassomos/imunologia , Interleucina-18/genética , Interleucina-1beta/genética , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR , Proteínas de Neoplasias/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/imunologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/virologiaRESUMO
The aim of this research was to study polymorphisms in the genes encoding cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with celiac disease (CD) antigens DQ2 (DQ2-positive) or DQ8 (DQ8-positive). We compared the results with healthy controls to determine whether any of the polymorphisms have a role in susceptibility to CD. A case-control of 192 patients with CD (96 DQ2-positive and 96 DQ8-positive) and 96 healthy controls from northeast Italy were included in the study. Analysis of single nucleotide polymorphisms (SNPs) was carried out using the polymerase chain reaction-restriction fragment length polymorphism method. Significant differences for the TNF-α(-308 G>A) polymorphism were observed when we compared the flowing groups: DQ2-positive with controls [odds ratio (OR) = 0.45, P = 0.0002]; DQ8-positive with controls (OR = 3.55, P < 0.0001); and DQ2-positive with DQ8-positive (OR = 0.12, P < 0.0001). We did not observe a statistically significant association between IL-6 (-174 G>C) polymorphism and CD (P > 0.05). Our results suggest that TNF-α(-308 G>A) polymorphism may play a role in susceptibility to CD in Italian patients.
Assuntos
Doença Celíaca/epidemiologia , Doença Celíaca/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Antígenos HLA-DQ/genética , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Investigations of any type of crime invariably starts at the crime scene by collecting evidence. Thus, the purpose of this research was to collect and analyze an entomological trace from an environment that is similar to those of indoor crime scenes. Hematophagous mosquitoes were collected from two residential units; saliva of volunteers that were residents in the units was also collected for genetic analysis as reference samples. We examined the allele frequencies of 15 short tandem repeat loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA) and amelogenin. A total of 26 female hematophagous mosquitoes were identified as Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus; we were able to obtain 11 forensically valid genetic profiles, with a minimum of 0.028203 ng/µL of human DNA. Thus, the results of this study showed that it was possible to correlate human genetic information from mosquitoes with the volunteer reference samples, which validates the use of this information as forensic evidence. Furthermore, we observed mixed genetic profiles from one mosquito. Therefore, it is clearly important to collect these insects indoors where crimes were committed, because it may be possible to find intact genetic profiles of suspects in the blood found in the digestive tract of hematophagous mosquitoes for later comparison to identify an offender and/or exclude suspects.
Assuntos
Culicidae/genética , DNA/sangue , Genética Forense , Repetições de Microssatélites/genética , Animais , Crime , Impressões Digitais de DNA , Feminino , Frequência do Gene , Testes Genéticos , HumanosRESUMO
Polymorphisms in interleukin (IL)-18, IL-12 and interferon (IFN)-γ genes are associated with different levels of cytokines expression and have been associated with rheumatoid arthritis (RA). IL-18 +105 A/C, IL-12B +1188 A/C and IFN-γ +874 T/A polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (PCR) and amplification refractory mutation system PCR from 90 RA patients and 186 healthy individuals. There were significant differences to IL-18 +105 A/C polymorphism between the RA and control groups (odds ratio = 3.77; P < 0.0001). Individual carriers of the variant allele C had a 3.77-fold increased risk of for RA (P = 0.0032). No association was observed for IL-12B and IFN-γ polymorphisms. Our finds suggest a possible role for IL-18 polymorphism in the RA susceptibility in studied population.
Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença , Interferon gama/genética , Subunidade p40 da Interleucina-12/genética , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Brasil , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Interferon gama/imunologia , Subunidade p40 da Interleucina-12/imunologia , Interleucina-18/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RiscoRESUMO
Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population.
Assuntos
Impressões Digitais de DNA/métodos , Genética Forense/métodos , Frequência do Gene/genética , Marcadores Genéticos/genética , Repetições de Microssatélites/genética , Brasil , Genética Populacional , Heterozigoto , Humanos , Paternidade , Reação em Cadeia da PolimeraseRESUMO
Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , População Negra/genética , Polimorfismo de Nucleotídeo Único , População Branca/genética , Indígena Americano ou Nativo do Alasca/etnologia , Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , População Negra/etnologia , População Negra/estatística & dados numéricos , Brasil , Feminino , Frequência do Gene , Genética Populacional/métodos , Genética Populacional/estatística & dados numéricos , Genótipo , Humanos , Masculino , População Branca/etnologia , População Branca/estatística & dados numéricosRESUMO
The aim of this study was to perform an association study between seven Fyn-binding protein gene (FYB)-tag single nucleotide polymorphisms (SNPs) and type I diabetes mellitus (T1DM), as well as with disease age of onset. We also assessed the role of FYB SNPs in the insurgence of autoimmune polyglandular syndrome type III (APSIII), characterized by the simultaneous presence of autoimmune thyroid disease and celiac disease, in patients with T1DM from a Northeastern Brazilian population. One hundred and seventy-seven patients with T1DM and 190 healthy individuals were genotyped for seven tag SNPs, covering most of the FYB locus, using real-time polymerase chain reaction amplification. There was no significant difference in the distribution of allele and genotype frequencies among patients and healthy individuals. Moreover, none of the tag SNPs were associated either to T1DM age of onset or to the insurgence of APSIII. However, since the FYB protein is a key component in T cell response, its gene variants might play a role in protein function, which might be testable in a population with different genetic backgrounds or by using functional assays.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , MasculinoRESUMO
This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5' upstream regulatory region (URR), 3' untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12% in SLE patients vs 6% in controls; odds ratio (OR), 2.10, 95% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8% in SLE patients and 6.3% in controls; OR, 2.14, 95% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is far from being elucidated yet, our association study results along with a systematic review and meta-analysis suggest that HLA-G might be able to slightly modulate the complex SLE phenotype (pooled OR, 1.14, 95% CI, 1.02-1.27, P = 0.021).
Assuntos
Antígenos HLA-G/genética , Lúpus Eritematoso Sistêmico/genética , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Adulto , Alelos , Autoanticorpos/sangue , Brasil , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-G/fisiologia , Haplótipos/genética , Humanos , Mutação INDEL , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Avaliação de SintomasRESUMO
Type 1 diabetes mellitus (T1D) is an organ-specific autoimmune disease characterized by T-cell mediated self-destruction of insulin-producing ß cells in the pancreas. T1D patients are prone to develop other glandular autoimmune disorders, such as autoimmune thyroid disease that occurs simultaneously with autoimmune polyglandular syndrome type III (APSIII). Signal transducer and activator of transcription 4 (STAT4) is a well-known regulator of proinflammatory cytokines, and interferon-induced with helicase C domain 1 (IFIH1) is activated in the interferon type I response. Both genes have been examined separately in autoimmune diseases and, in this study, we assessed their joint role in T1D and APSIII. We conducted a case-control study, enrolling 173 T1D patients and 191 healthy controls from northeastern Brazil, to assess the distribution of the rs7574865 and rs3024839 SNPs in STAT4 and the rs3747517 and rs1990760 SNPs in IFIH1 in T1D and APSIII patients. Additionally, we conducted a meta-analysis with the rs7574865 SNP in STAT4 (1392 T1D patients and 1629 controls) and the rs1990760 SNP in IFIH1 (25092 T1D patients and 28544 controls) to examine their association with T1D. Distribution of STAT4 and IFIH1 allelic frequencies did not show statistically significant differences between T1D patients and controls in our study population; however, the meta-analysis indicated that SNPs in STAT4 and IFIH1 are associated with T1D worldwide. Our findings indicate that although STAT4 and IFIH1 SNPs are not associated with T1D in a Brazilian population, they might play a role in susceptibility to T1D on a larger worldwide scale.