Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women

We assessed the effect of two common mutations in the lipoprotein lipase ge ne (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1144 women from the Framingham Offspring Study (FOS ) were analyzed for these two LPL variants. Subsequently, the association w ith fasting plasma lipids and risk of coronary artery disease (CHD) was det ermined. We extended our study by calculating weighed means of lipids and l ipoproteins in carriers and non-carriers for these LPL mutations in patient s with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower hig h-density lipoprotein-cholesterol (HDL-C) (Delta = -0.07 mmol/l, p = 0.03) and a trend towards increased triglycerides (Delta = 0.25 mmol/l, p = 0.07) . In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (Delta = -0.02 mmol/l for HDL-C and Delta = 0.14 mmol/l for triglyc erides, respectively). Cumulative analysis of other studies of male carrier s of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60 (1.85) mmol/l vs. 1.62(1.18) mmol/l: p < 0.0001) (D9N; 1.94 (1.19) mmol/l v s. 1.74(1.17) mmol/l: p < 0.001) and lower HDL-C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p < 0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) m mol/l: p < 0.0001). In females, results differed with higher TG levels (N29 1S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mm ol/l vs. 0.96(0.51) mmol/l: p < 0.01) and lower HDL-C levels (N291S; 1.27(0 .33) mmol/l vs. 1.51(0.32) mmol/l: p < 0.0001); however, the HDL-C levels f or D9N carriers were similar to non-carriers (D9N; 1.52(0.29) mmol/l vs. 1. 53(0.35) mmol/l: p = 0.83). Our data provide evidence that common variants of the LPL gene are signific ant modulators of lipid and lipoprotein levels in both men and women.