Predictive role of polymorphisms in interleukin-5 receptor alpha-subunit, lipoprotein lipase, integrin A2 and nitric oxide synthase genes on ischemic stroke in type 2 diabetes—An 8-year prospective cohort analysis of 1327 Chinese patients

• Published in: Atherosclerosis 2011-03, Vol.215 (1), p.130-135
• Main Authors: Luk, Andrea O.Y, Wang, Ying, Ma, Ronald C.W, Tam, Claudia H.T, Ng, Maggie C.Y, Lam, Vincent, Yang, Xilin, Baum, Larry, Tong, Peter C.Y, Chan, Juliana C.N, So, Wing-Yee
• Format: Article
• Language: English
• Subjects: Aged; Asian Continental Ancestry Group - genetics; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cohort Studies; confidence interval; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; endothelial nitric oxide synthase; Female; genes; Genetic polymorphisms; Genetic Predisposition to Disease; Humans; inflammation; Integrin alpha2 - genetics; integrins; interleukin-5; Interleukin-5 Receptor alpha Subunit - genetics; lipoprotein lipase; Lipoprotein Lipase - genetics; Male; Medical sciences; Middle Aged; Neurology; Nitric Oxide Synthase Type III - genetics; noninsulin-dependent diabetes mellitus; patients; Polymorphism, Single Nucleotide; regression analysis; risk; Risk Factors; single nucleotide polymorphism; Stroke; Stroke - etiology; Stroke - genetics; Type 2 diabetes; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2010.11.042

Abstract Objective Ischemic stroke is prevalent in type 2 diabetes and may be due to metabolic, vascular and inflammatory factors. Genetic variants implicated in these pathways may have joint effects on stroke risk. In this proof-of-concept study, we examined gene–gene interactions on risk of incident ischemic stroke in an 8-year prospective cohort of Chinese type 2 diabetic patients. Methods Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for cardiovascular disease and inflammation were genotyped in 1327 patients with no past history of ischemic stroke. The association of SNPs with stroke was tested using Cox proportional hazard regression analysis. Permutation procedure was performed to control for multiple statistical comparisons. Results Genetic variants including A/A of IL5RA (interleukin-5 alpha subunit) -5091G > A, X/X of LPL (lipoprotein lipase) S447X, A/A of ITGA2 (integrin A2) G873A and T/T or G/T of NOS3 (endothelial nitric oxide synthase) G894T showed significant correlations with incident ischemic stroke. The hazard ratios (HR) increased with number of genetic risk factors reaching an adjusted HR (confidence interval) of 3.68 (1.78–7.62, P = 4.4 × 10−4 ) in those with ≥2 genetic risk factors compared to those without. Conclusion Polymorphisms in IL5RA , LPL , ITGA2 and NOS3 genes were independently associated with ischemic stroke in Chinese diabetic population.