Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids

Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Three recently described exonic polymorphisms of the gene, D9N, N291S and S447X, have been variably found to influence plasma lipids while effects on coronary heart disease (CHD) are less well documented. Two predominantly Caucasian groups were studied: CHD patients 2. There were, generally, trends to more adverse fasting plasma high-density lipoprotein (HDL) cholesterol and triglycerides in carriers of the 291S and 9N alleles, and the opposite trends for triglycerides in 447X carriers. In the community group, male carriers of 291S (n = 13) had significantly (20%) lower HDL cholesterol than corresponding non-carriers (n = 323), 0.98 +/- 0.07 mmol/l (mean +/- S.E.) versus 1.22 +/- 0.02 mmol/l (P <0.005), while HDL cholesterol was not different in male carriers (n = 8) and non-carriers (n = 296) of 9N (1.23 0.13 mmol/l versus 1.22 +/- 0.02 mmol/l). Multivariate analysis confirmed that the 291S allele carrier status: conferred a significantly lower HDL cholesterol (P = 0.001) and the 447X allele lower triglyceride (P <0.01) in the community group. In conclusion, LPL 9N carrier status was unequivocally related to premature CHD and to MI in males, strongly supporting recent results in older aged males. The somewhat different effects of the D9N and N291S polymorphisms on plasma lipids, and the absence of a clear effect of the N291S on CHD, raise the possibility that the effect of 9N carrier status might be mediated through effects on LPL function in addition to those influencing fasting plasma lipids. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.