Abstract

Polymorphism in Renin-Angiotensin-Aldosterone System (RAAS) genes have been studied extensively in various ethnic groups and largely with inconsistent findings on relationship with the risk of developing type 2 diabetes mellitus (T2DM). In this study, we investigated the association of Insertion/Deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) and -344 C/T polymorphism of aldosterone synthase [cytochrome P450 (CYP11B2)] with T2DM in an Emirati population and interactive effects between these two gene polymorphisms on T2DM risk. A total of 243 Emirati subjects (133 healthy control and 110 T2DM patients) were selected for the study. The ACE genotypes were determined by polymerase chain reaction (PCR) followed by agarose gel electrophoresis. The CYP11B2 genotyping was performed by PCR- Restriction Fragment Length Polymorphism Analysis(RFLP). ACE genotypes were not associated with T2DM risk. The frequencies of D allele were 0.68 and 0.64 in the patients and healthy group respectively and the differences were not statistically significant. For CYP11B2 -344C/T polymorphism, CC genotype was found significantly higher in healthy subjects than in T2DM patients (22.1 Vs 9.8%, p=0.016). The subjects with CC genotype were at decreased T2DM risk in the recessive model [Odd ratio 0.38 (0.17-0.84)].  An interactive effect on T2DM risk was found between ACE-ID and CYP11B2 -CC genotypes. In the subjects with combination of ID + CC genotypes, risk of T2DM was further reduced (odd ratio 0.05 vs 1.12). The association of CC with T2DM was independent of age and gender. To date, this study is the first report on association of CYP11B2 -344C/T with T2DM and its possible interaction with ACE I/D polymorphism in an Emirati population. The results suggest that ACE I/D polymorphism does not affect T2DM risk independently however, subjects with CC genotypes either alone or in combination with ACE  I/D heterozygote would be at decreased risk of developing T2DM.

Key words:  Type 2 diabetes mellitus, CYP11B2, Renin-Angiotensin-Aldosterone System, angiotensin converting enzyme, genetic polymorphism