Gene polymorphisms of fibronectin rs2289202 and fibrillin 2 rs331069 associate with vascular disease, the TAMRISK study

Abstract

Cell surface heparan sulfate (HS) proteoglycans interact with other extracellular matrix (ECM) components, and HS-binding regions are present in ECM proteins such as fibronectin and fibrillin. Because of their previously established role in susceptibility to intracranial aneurysms, the authors sought to determine whether polymorphisms of fibronectin (FN1, rs2289202) and fibrillin 2 (FBN2, rs331069) associate with selected cardiovascular risk factors and events in the TAMRISK study. A 50-year-old Finnish cohort of 810 subjects of whom 340 had diagnosed hypertension was analyzed. Samples were genotyped for FN1 rs2289202 and FBN2 rs331069 polymorphisms. Incidence of myocardial infarction (I21-I22), transient cerebral ischemic attacks (TIA, G45) and cerebrovascular diseases (I60-I69) were followed up until the subjects were on the average 60 years old. Subjects with FN1 rs2289202 (G>A) minor genotype AA had significantly more cerebrovascular disease than those with the G allele [P<0.001, odds ratio (OR), 8.73; confidence index (CI), 2.79-27.31], although those with the A allele had lower body mass index (P=0.008). Subjects with fibrillin rs331069 (T>C) minor genotype CC had more atherothrombotic disease (P=0.012, OR, 3.16; CI, 1.29-7.71), as measured by combined myocardial infarction and TIA, than those with the T allele. The gene polymorphisms for fibronectin and fibrillin 2 appear to associate with vascular disease.