NPC - LINKS TO DYSLIPIDEMIA BUT NOT CARDIOVASCULAR RISK

Abstract

Following our previous studies showing increased cardiovascular disease (CVD) risk and dyslipidemia in Niemann-Pick A and B carriers we assessed if CVD and dyslipidemia are increased in carriers and affected patients for Niemann-Pick type C (NPC) compared to the normal population. CVD in parents (n = 33) and first degree relatives of NPC patients (n = 56) was assessed using a validated CVD questionnaire. Fasting plasma lipoprotein profiles (total cholesterol and triglyceride (TG), LDL-cholesterol and HDL-cholesterol levels) were assessed in 58 individuals (40 heterozygous, 15 male, 25 female; and 17 homozygous, 8 female, 9 male). Of 33 heterozygous only 1 had history of stroke and none had history of myocardial infarct (MI). Of 56 grandparents 7 had a history of stroke and 9 had a history of MI, but only 1 had a history of premature MI (age 54). In heterozygote carriers mean total cholesterol levels and mean LDL-C levels were abnormally high (>200 mg/dl for cholesterol and >130 mg/dl for LDL-C). Surprisingly 18/40 heterozygous had abnormally elevated TG levels for this age group (>150 mg/dl). HDL-C levels were low (<40 mg/dl) in 6/40 heterozygote carriers No correlation was found between BMI and TG levels in the heterozygous subjects. In the homozygous NPC patients mean total cholesterol and LDL-C levels were normal for age. HDL-C was low (<40 mg/dl) in 53% and 47% had high TG for age (>130 mg/dl). These results indicate that NPC affected patients and carriers have abnormal lipid profiles, but despite dyslipidemia there is no evidence for increased cardiovascular risk in NPC carriers. We hypothesize that NPC genotypes link to abnormalities in TG and/or HDL metabolism.