Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction:: a population-based neuropathological study

BACKGROUND. Variants of the lipoprotein lipase (LPL) gene have been shown to influence serum lipid levels, risk of coronary heart disease and, as found recently, risk of clinical ischaemic cerebrovascular disease. Here we tested for an association between brain infarction and two common polymorphisms of the LPL gene, Ser447Ter and Asn291Ser. METHOD. To avoid ascertainment and selection bias involved in many association studies, we compared the distribution of these polymorphisms in neuropathologically verified patients (n = 119) vs controls (n = 133) derived from a prospective, population-based study (the Vantaa 85+ study). RESULTS. The LPL Ter447 variant was negatively associated with neuropathologically verified brain infarcts (P = 0.006), and even more strongly with small brain infarcts (P = 0.004). In addition, we found that the Ter447 variant was associated with higher serum HDL cholesterol (P = 0.004) and lower triglyceride levels (P = 0.003), and that it was negatively associated with pathologically verified severe coronary artery disease (P = 0.001) in the Vantaa 85+ study sample. The Asn291Ser polymorphism was not significantly associated with brain infarction. CONCLUSION. The Ter447 variant of LPL is associated with decreased risk of brain infarction and coronary artery disease in our very elderly population.