Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil.

Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-Δ32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-Δ32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-Δ32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.

Study of polymorphic variants of the serotonin 2A receptor gene (5-HT2A) and its possible effects on smoking habits of a population from northeastern Brazil.

Previous studies have revealed a genetic component, including genetic polymorphisms in the serotonergic pathway, particularly in the serotonin receptor gene (5-HT2A). The aim of this study was to investigate associations of the T102C (rs6313) and A-1438G (rs6311) polymorphisms with tobacco use in a population from northeastern Brazil. We evaluated these polymorphisms in 135 nonsmokers and 135 smokers using polymerase chain reaction-restricted fragment length polymorphism. The distribution of allele and genotype frequencies and associations of polymorphisms with smoking were assessed with the chi-squared (χ(2)) test, the Fisher exact test, and odds ratio (OR) with a 95% confidence interval (CI). There were no differences in the distribution of genotype and allele frequencies between nonsmokers and smokers for A-1438G (P = 0.80) and T102C (P = 0.35). However, these polymorphisms were significantly associated with habit frequency (A/G: P = 0.02, OR = 6.87, 95%CI = 1.23-38.31, P = 0.04; A/G+G/G: P = 0.04, OR = 3.67, 95%CI = 1.06-12.75, P = 0.07), age of onset (C/C: P = 0.02, OR = 3.26, 95%CI = 1.17-9.07, P = 0.03, and nicotine dependence level (A/G: P = 0.02, OR = 3.28, 95%CI = 1.17-9.18, P = 0.04; A/G+G/G: P = 0.04, OR = 2.81, 95%CI = 1.13-6.99, P = 0.04; T/C: P = 0.03, OR = 3.12, 95%CI = 1.13-8.57, P = 0.04; T/C+C/C: P = 0.02, OR = 3.06, 95%CI = 1.22-7.70, P = 0.02). Therefore, these polymorphisms may not contribute significantly to smoking initiation, they do appear to be associated with habit maintenance.

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil.

Approximately 200 million people suffer from type 2 diabetes (T2D) worldwide, and the rapid increase in the prevalence of this disease is likely a result of multiple environmental factors, such as increased food intake and decreased physical activity in genetically predisposed individuals. Different population studies have demonstrated a strong association of two polymorphic variations in the TCF7L2 gene, the noncoding single nucleotide polymorphisms (SNPs) rs7903146 (C/T) and rs12255372 (G/T), with T2D. Herein, we analyzed the association of these SNPs with T2D in a population from northeastern Brazil. Our results showed that the genotype and allele frequencies in TCF7L2 rs7903146 and rs12255372 were similar in the patient and control groups (P > 0.05). In addition, the allele frequencies were not significantly associated with T2D risk [rs7903146: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.52-1.76, P = 1.00, and rs12255372: OR = 1.38, 95%CI = 0.72-2.62, P = 0.41]. These data suggest that the TCF7L2 SNPs rs7903146 and rs12255372 may not significantly contribute to T2D susceptibility in this population. However, our results may reflect the small number of subjects. Alternatively, these results may be attributable to specific ethnic effects, as most of the previously reported associations were demonstrated with predominantly European populations. To reach a definitive conclusion on the role of such gene variants for T2D in mixed populations, additional efforts are necessary to replicate this study with larger populations from areas with more ethnic heterogeneity.

Prevalence of variants that confer risk for venous thromboembolism in an elderly population of northeastern Brazil.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality stemming from cardiovascular disease. It is a multifactorial disease caused by a combination of acquired risk factors, of which advanced age is the most significant, and genetic factors, including the variants FV G1691A, FII G20210A, and MTHFR C677T. We estimated the prevalence of these genomic variants in an elderly population of northeastern Brazil. The study included 188 elderly persons (65-93 years), of which 68 (36.2%) were men and 120 (63.8%) were women. Variants were detected by polymerase chain reaction-restriction fragment length polymorphism analysis, and subsequent electrophoresis on an 8% polyacrylamide gel stained with silver nitrate. The study population was in Hardy-Weinberg equilibrium for the 3 loci. Of the individuals analyzed, none carried variants of FV or FII (0%), and 24.7% had the MTHFR C677T polymorphism: 59 subjects (31.4%) were heterozygous (CT) and 17 subjects (9%) were homozygous (TT). Based on the analysis of these particular genes, we conclude that the study population does not present an increased risk for the development of VTE. Faced with a growing aging population worldwide, similar studies in other countries will help in the prevention of VTE in older individuals.

Prognostic value of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms and the susceptibility to gliomas in individuals from Southeast Brazil.

The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.

Prognostic value of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms and the susceptibility to gliomas in individuals from Southeast Brazil

The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.