Genotypic interactions of renin-angiotensin system genes with diabetes type 2 in a Tunisian population

Aims: To explore the role of genetic variants of angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), and angiotensin type 1 receptor (AT1R A1166C) as predictors of diabetes risk and to examine their combined effects on type 2 diabetes mellitus (T2DM) patients. Main methods: One hundred and fourteen T2DM patients were compared to 175 healthy controls with similar age and sex. Key findings: The genotypic frequencies for all three genes alone were significantly associated with increased risk of developing diabetes. Logistic regression analysis of classic coronary risk factors and the genetic polymorphisms demonstrated that hypertension and ACE DD genotype were the most significant contributors to T2DM. For the renin-angiotensin system (RAS) genes, the risk of T2DM in individuals with one risk genotype was 1.9 (95%CI: 1.1-3.0, p=0.017) higher than those with zero risk genotype. Individuals who carried two risk genotypes had a 4.0 (95%CI 1.7-9.4, p=0.001) times higher risk of T2DM than those who did not carry any risk genotypes of the RAS genes. Most interestingly, the risk of T2DM for individuals with three risk genotypes was 26.2 (95%CI: 5.8-117.9, p<0.001) higher than those with zero risk genotype. Significance: The results of the present study imply that genotyping of renin-angiotensin system genes could become an important part of the clinical process of risk identification for T2DM in Tunisian population. © 2010 Elsevier Inc.