title: 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.
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.
  
  
  CONCLUSIONS
  Polymorphisms in IL5RA, LPL, ITGA2 and NOS3 genes were independently associated with ischemic stroke in Chinese diabetic population.
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Andrea O Y
authors.initials: AO
authors.lastname: Luk
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ronald C W
authors.initials: RC
authors.lastname: Ma
authors.forename: Claudia H T
authors.initials: CH
authors.lastname: Tam
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Vincent
authors.initials: V
authors.lastname: Lam
authors.forename: Xilin
authors.initials: X
authors.lastname: Yang
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.forename: Peter C Y
authors.initials: PC
authors.lastname: Tong
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: So
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D053666:Interleukin-5 Receptor alpha Subunit / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics*
chemical_list: C485918:IL5RA protein, human; D039421:Integrin alpha2; D053666:Interleukin-5 Receptor alpha Subunit; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D008071:Lipoprotein Lipase