LDL receptor mutations and ApoB mutations are not risk factors for ischemic cerebrovascular disease of the young, but lipids and lipoproteins are

Background: The genetic background for ischemic cerebrovascular disease of the young and the role of lipids and lipoproteins as risk factors are not c lear. Methods: We determined five LDL receptor mutations (Trp23Stop, Trp66G ly, Trp556Ser, 313+1G --> A, 1846-16 --> A) and three apolipoprotein B muta tions (Arg3500Gln, Arg3500Trp, Arg3531Cys), and other risk factors for isch emic cerebrovascular disease in 80 patients (36 women, 44 men) with onset o f disease before the age of 50 years compared with 3366 individuals from a general population sample within the same age range. Results: None of the p atients were carriers of mutations in the LDL receptor (Trp23Stop, Trp66Gly , Trp556Ser, 313+1G --> A, 1846 - 1G --> A) or the apolipoprotein B gene (A rg3500Gln, Arg3500Trp, Arg3531Cys) associated with hypercholesterolemia. Ho wever, on univariate analysis as well as on logistic regression analysis al lowing for age and gender, plasma cholesterol (OR 1.4; P < 0.0005), HDL-cho lesterol (OR 0.4; P< 0.005), diabetes (OR 5.8; P < 0.0001), and hypertensio n (OR 3.9; P< 0.001) were significant predictors of ischemic cerebrovascula r disease. Conclusions: The five most common LDL receptor mutations in Dani sh patients with familial hypercholesterolemia and three mutations in the a polipoprotein B gene did not predispose to ischemic cerebrovascular disease of the young. However, cholesterol and HDL-cholesterol are important risk factors for ischemic cerebrovascular disease of the young in the present st udy. The elevation in cholesterol could in some patients be due to rare LDL receptor mutations not tested for, and could in other patients be multifac torial in origin. fur J Neurol 6:691-696 (C) 1999 Lippincott Williams & Wil kins.