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
- Colin N.A. Palmer1,
- Charlotte H. Kimber1,
- Alex S.F. Doney2,
- Anna S. Proia3,
- Andrew D. Morris2,
- Eleonora Gaetani3,
- Miriam Quarta3,
- Roy C. Smith4 and
- Roberto Pola3,4
- 1Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, U.K.;
- 2Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, U.K.;
- 3Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy;
- 4Division of Cardiovascular Research, Department of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
- Corresponding author: Roberto Pola, .
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.
RESEARCH DESIGN AND 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.
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See accompanying commentary, p. 2729.
- Received November 16, 2009.
- Accepted June 23, 2010.
- © 2010 by the American Diabetes Association.
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