Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese

Background and Purpose-Lipid and lipoprotein abnormalities have been implic ated in the pathogenesis of ischemic cerebrovascular disease and atheroscle rosis, Lipoprotein lipase (LPL) plays an important role in plasma lipoprote in metabolism. Several studies have recently reported the presence of a rel ationship between Ser447Stop mutation of LPL and coronary artery disease. O ther polymorphisms (HindIII and PvuII) of the LPL gene have already been sh own to correlate significantly with dyslipidemia. We investigated whether t hese polymorphisms are associated with increased risk of ischemic cerebrova scular disease (CVD). Methods-We recruited 177 CVD patients (atherothrombotic infarction, n=71; c ardioembolic infarction, n=30; lacunar infarction, n=76) and 177 healthy co ntrol subjects. Subjects were genotyped for the Ser447Stop mutation and for HindIII/PvuII restriction fragment length polymorphisms of the LPL gene, a nd the findings were investigated for associations with the clinical subtyp es of CVD and with lipid levels. Results-The Ser447Stop mutation correlated significantly with CVD (0.107 ve rsus 0.158; P=0.035). For the CG+GG versus CC genotype, the odds ratio betw een control subjects and CVD patients with atherothrombotic infarction was 0.42 (95% CI, 0.18 to 0.99) (P=0.046). Serum HDL cholesterol and triglyceri de levels did not correlate significantly with the Ser447Stop genotype, Hin dIII polymorphism correlated significantly with CVD (0.234 versus 0.169; P= 0.031), but the frequency of PvuII polymorphism was not significantly diffe rent between groups. Conclusions-Our results suggest that the Ser447Stop mutation of the LPL gen e is a novel genetic marker for low risk of atherothrombotic cerebral infar ction.