Ras Gene Polymorphism And Nanjing Han Type 2 Diabetic Dyslipidemia

Objective:Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in cardiovascular diseases. However, to the best of our knowledge, the relation between RAS gene polymorphisms and the dyslipidemia in type 2 diabetes (T2D) patients have not been analyzed. Because of this, the present study was performed to investigate whether the angiotensin I converting enzyme (ACE) (insertion/deletion, or I/D), angiotensinⅡtype 1 receptor (AT1R) (rs5186), and ACE2 (rs2285666) polymorphisms were associated with the dyslipidemia in T2D patients of Nanjing Han origin.Design and Methods:A case-control study was performed. A total of 788 subjects from Nanjing were recruited, which include 282 consecutive patients with type 2 diabetes and dyslipidemia (Group A),182 patients with type 2 diabetes but without dyslipidemia (Group B), and 324 healthy controls without diabetes or dyslipidemia. the ACE (I/D), AT1R (rs5186) and ACE2 (rs2285666) polymorphisms were examed by polymerase chain reaction(PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. The association between a certain polymorphism and each group was assessed by odds ratio (OR).Results:The D allele of the ACE (I/D) was significantly associated with the risk of T2D accompanying dyslipidemia between group A and controls (OR=1.37,95% CI=1.08-1.74; P=0.010), and significant association of the D allele with dyslipidemia was also observed in diabetic patients (OR=1.88,95% CI=1.40-2.54; P<0.001). Furthermore, the ID genotype had a decreased risk of developing T2D without dyslipidemia as compared with controls (OR=0.52,95% CI=0.32-0.82; P=0.0060). The distributions of the AT1R (rs5186) and ACE2 (rs2285666) genotypes and alleles did not differ between T2D patients with or without dyslipidemia and the controls. Combined analysis between ACE and AT1R, ACE and ACE2 gene polymorphisms showned that individuals carrying both ACE ID/DD and ATIR AC genotypes or both ACE ID/DD and ACE2 GA/AA genotypes increased susceptibility to dyslipidemia (OR=2.13,95% CI=1.39-3.26; P<0.001 and OR=12.13,95% CI=2.55-57.69; P=0.0017) in T2D patients. Finally, there was significant difference of ACE activity between T2D patients with different ACE (I/D) genotypes, and the ACE activity of ID and DD genotype in group A was significantly higher when compared to group B.Conclusions:This study demonstrates that the ACE (I/D) polymorphism is associated with T2D in Nanjing Han population, regardless of the absence or presence of dyslipidemia, and that diabetic patients with ACE (I/D) D allele seem to be more susceptible to dyslipidemia. The polymorphisms in the AT1R (rs5186) and ACE2 (rs2285666) seem to play lesser roles in the development of T2D. There may exist co-effective action between ACE and AT1R gene, ACE and ACE2 gene in T2D with dyslipidemia. Finally, the dyslipidemia in T2D patients is related with ACE activity.