Associação entre os polimorfismos rs7903146 no gene TCF7L2 e rs2287019 no gene GIPR e diabetes mellitus tipo 2 em indivíduos com síndrome metabólica

Abstract

Metabolic syndrome (MetS) is a progressive disturb that eventually may lead to type 2 diabetes mellitus (T2DM) in genetically susceptible individuals. Genetic studies show that single nucleotide polymorphisms (SNPs) in genes involved in glucose and lipid metabolic pathways are related to high predisposition to develop MetS and T2DM. However, there are few studies associating SNPs, MetS and T2DM in Brazil, especially in regions whose population is highly miscegenated. Thus, the aim of the present study was to investigate the association between SNPs rs7903146 in the TCF7L2 gene and rs2287019 in the GIPR gene and T2DM in MetS individuals. It is a cross-sectional case-control study, and the study sample was composed of 236 subjects, aged 40 years or more. Every subject had the MetS diagnosis, according to the criteria of the International Diabetes Federation. The case group consisted of 178 T2DM individuals, and the control group had 58 subjects without diabetes or altered fasting glycemia. The genotypes were determined by real-time polymerase chain reaction technique. Pearson's chi-square test, Fisher's exact test, Student's t test, Mann-Whitney U test, and Kruskal-Wallis test and Variance Analysis (ANOVA) were used to compare variables between groups and the genotype frequencies of the studied SNPs. The genotype and allele frequencies of rs7903146 did not differ between the study groups (p = 0.250 and p = 0.120, respectively). Regarding rs2287019, subjects with the heterozygous genotype had increased odds to develop T2DM (OR = 11.92, 95% CI 1.47-96.39, p = 0.020). Significant differences were found between the rs7903146 genotypes for fasting glycemia, fasting insulin, HOMA-β and triglycerides in MetS patients with T2DM. No significant difference was detected among rs2287019 genotypes and the demographic, clinical, anthropometric and biochemical variables in the whole study sample, except for total cholesterol (p = 0.042). In conclusion, carriers of the GIPR rs2287019 CT genotype have increased risk to develop T2DM, which suggests that alterations in the action of incretins may play an important role in the pathophysiology of T2DM in MetS individuals. There was no association between the TCF7L2 rs7903146 polymorphism and risk of T2DM in this population group, suggesting that this SNP is not associated with T2DM in Northeast Brazilian miscegenated population. However, further studies with a large study sample are required to confirm these results.