title: Combined effect of inflammatory gene polymorphisms and the risk of ischemic stroke in a prospective cohort of subjects with type 2 diabetes: a Go-DARTS study.
abstract: OBJECTIVE
  We have previously observed that genetic profiles determined by the combination of five functionally significant single nucleotide polymorphisms (SNPs) (rs1800795, rs5498, rs5361, rs1024611, and rs679620) of genes encoding prototypical inflammatory molecules are associated with history of ischemic stroke. Here we tested the ability of this multigenic model to predict stroke risk in a large population-based prospective cohort of subjects with type 2 diabetes.
  
  
  METHODS
  This study was conducted using a prospective cohort of individuals with type 2 diabetes participating in the Go-DARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) study, which includes genetic and clinical information of patients with diabetes within the Tayside region of Scotland, U.K. The above-mentioned inflammatory SNPs were investigated in 2,182 Go-DARTS participants. We created an inflammatory risk score (IRS), ranging from 0 to 5, according to the number of "at-risk" genotypes concomitantly carried by a given individual. The primary outcome was the occurrence of fatal or nonfatal stroke of any kind. Mean follow-up time was 6.2 ± 1.1 years.
  
  
  RESULTS
  The incidence of stroke increased according to the IRS. The IRS was significantly and independently associated with increased stroke risk after adjustment for other conventional risk factors (hazard ratio 1.34 [95% CI 1.1-1.7]; P = 0.009). The highest hazard ratio for stroke was found in subjects concomitantly carrying > 3 proinflammatory variations and in subjects without previous cardiovascular diseases.
  
  
  CONCLUSIONS
  This large prospective cohort study provides evidence that SNPs of genes encoding prototypical inflammatory molecules may be used to create multigenic models that predict stroke risk in subjects with type 2 diabetes.
authors.affiliation: Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Kimber
authors.forename: Alex S F
authors.initials: AS
authors.lastname: Doney
authors.forename: Anna S
authors.initials: AS
authors.lastname: Proia
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gaetani
authors.forename: Miriam
authors.initials: M
authors.lastname: Quarta
authors.forename: Roy C
authors.initials: RC
authors.lastname: Smith
authors.forename: Roberto
authors.initials: R
authors.lastname: Pola
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics