Does a null mutation in the APOC3 gene improve plasma lipid profiles and prevent subclinical atherosclerosis in the Lancaster Amish?
A null mutation in the APOC3 gene is associated with a favorable lipid profile and reduced subclinical atherosclerosis, suggesting that lifelong deficiency of apoC-III is cardioprotective.
Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.
Pollin et al. (Fri,) studied this question.