ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. METHODS: 275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS: ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P < 0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P < 0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P < 0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P < 0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P < 0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS) ≥ 50% (both P < 0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P < 0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P < 0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P < 0.05). CONCLUSION: ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.