IL-10 (-819C/T), TNFA (-30G/A) and ENOS (-786T/C) Polymorphisms Modulating the Outcome Related to Mental Disorders in Crack Addicted Users.

Background: Cocaine/crack use affects immune system molecules and development of mental disorders has been identified. Objective: To investigate the relationship of polymorphisms in the TNFA (-308G/A), IL-10 (-819C/T) and ENOS (-786T/C) genes with mental disorders in cocaine and crack users. Methods: A case-control study was carried out, which included 107 cocaine and crack users and 115 controls who never used healthy cocaine and crack. The SNPs in the TNFA (-308G/A), IL-10 (-819C/T) and ENOS (-786T/C) genes were genotyped by real time PCR. Results: As for the individuals included in this study, the average age of 31.4 years (± 8.59). We identified that the G/A genotype to TNFA (-308) (OR = 0.24; p = 0.03) and the A allele (OR = 0.30; p = 0.03) were associated with reduced risk for dysthymic disorder. The T allele of the IL-10 (-819) polymorphism was associated with decreased risk of developing panic disorder (OR = 0.44; p = 0.01), while the C allele was correlated with an increased risk for alcohol dependence (OR = 1.97; p = 0.04), alcohol abuse (OR = 1.81; p = 0.04) and psychotic syndrome (OR = 2.23; p = 0.01). C/C genotype was correlated with increased chances of developing current psychotic syndrome (OR = 4.23; p = 0.01). Conclusion: Our results suggest that genetic polymorphisms promote susceptibility or promote protection for clinical phenotypes of psychiatric comorbidities in cocaine and crack users and be considered as good prognostic markers.

The Role of the IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) Polymorphisms of Impulsive and Aggressive Personality Traits in Cocaine/Crack Users.

Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms were determined by Real-Time PCR. In addition, the relationship between these polymorphisms and Impulsivity and Aggression was determined. We found that the physical aggressiveness sub score was negatively correlated with the C allele of -819C/T polymorphism of the IL-10 (b = -0.14; p = 0.04). The T allele of the SNP -786T/C of the ENOS gene positively predicts traits of physical aggressiveness (b = 0.14; p = 0.04). The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of -308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.

Prevalence of IGFBP3, NOS3 and TCF7L2 polymorphisms and their association with hypertension: a population-based study with Brazilian women of African descent.

OBJECTIVE: African ancestry seems to be a risk factor for hypertension; however, few genetic studies have addressed this issue. This study aimed to investigate the prevalence of polymorphisms NOS3; rs1799983, IGFBP3; rs11977526 and TCF7L2; rs7903146 in Brazilian women of African descent and their association with hypertension. RESULTS: The prevalences of the less frequent genotypes were 26.5% TT genotype of NOS3; rs1799983, 16.7% AA genotype of IGFBP3; rs11977526, and 18.3% TT genotype of TCF7L2; rs7903146. For these conditions, the prevalence of hypertension and PR (adjusted) relatively to the ancestral genotype were, respectively: 52.0% vs 24.5% (PR = 1.54; p < 0.001), 62.0% vs 24.1% (PR = 1.59; p < 0.001), and 38.9% vs 27.9% (PR = 0.86; p = 0.166). Associations with hypertension were statistically significant, except for the TCF7L2; rs7903146 polymorphism, after adjusted analysis. Brazilian Afro-descendant women with the TT genotype for the NOS3 gene and the AA genotype for the IGFBP3 gene are more susceptible to hypertension. The understanding of underlying mechanisms involving the pathogenesis of hypertension can motivate research for the development of new therapeutic targets related to nitric oxide metabolism and the management of oxidative stress.

Prevalence of endothelial nitric oxide synthase (ENOS) gene G894T polymorphism and its association with hypertension: a population-based study with Brazilian women.

INTRODUCTION: Hypertension is one of the most prevalent diseases in the world, accounting for millions of deaths each year. The reduction in the concentration of nitric oxide (NO) produced by the catalysis of endothelial nitric oxide synthase (eNOS) is associated with higher blood pressure (BP) levels. This reduction might be because of genetic polymorphisms. This study investigated the prevalence of the eNOS gene G894T polymorphism in women from northeast Brazil and its association with hypertension. MATERIAL AND METHODS: This cross-sectional study included 810 women (aged 19-49 years). Sociodemographic, health, anthropometric, and BP data were collected. Hypertension was defined according to the following criteria: systolic BP ≥ 140 mm Hg, diastolic BP ≥ 90 mm Hg, the regular use of antihypertensive medication, or some combination thereof. Epithelial cells from the cheek mucosa were obtained for DNA extraction. Genotyping was performed via real-time PCR. The measure of association was the prevalence ratio (PR) and its 95% CI as calculated via Poisson regression. RESULTS: The frequencies of the GG, GT, and TT genotypes were 57.1%, 35.7%, and 7.2%, respectively. For each of these genotypes, the prevalence of hypertension in women was 17.9%, 23.6%, and 34.4%, respectively. Relative to the GG genotype, the PRs after adjusting for cofounding factors were 1.24 (95% CI: 0.95-1.61, p = 0.11) for GT and 1.76 (95% CI: 1.16-2.67, p < 0.01) for TT. CONCLUSIONS: The T allele of the G894T polymorphisms is associated with hypertension in women. This may have implications for prevention and treatment.