title: Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women.
abstract: We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1 144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non-carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower high-density lipoprotein-cholesterol (HDL-C) (delta = - 0.07 mmol/ 1, p = 0.03) and a trend towards increased triglycerides (delta = 0.25 mmol/ 1, p = 0.07). In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (delta = - 0.02 mmol/1 for HDL-C and delta = 0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers 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 vs. 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) mmol/l: p < 0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mmol/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 for 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 significant modulators of lipid and lipoprotein levels in both men and women.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. johnjpk@worldonline.nl
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: M E
authors.initials: ME
authors.lastname: Wittekoek
authors.forename: S N
authors.initials: SN
authors.lastname: Pimstone
authors.forename: W F
authors.initials: WF
authors.lastname: Wilson
authors.forename: S E
authors.initials: SE
authors.lastname: Gagné
authors.forename: M G
authors.initials: MG
authors.lastname: Larson
authors.forename: E J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: J M
authors.initials: JM
authors.lastname: Boer
authors.forename: C
authors.initials: C
authors.lastname: Gerdes
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008055:Lipids; D014280:Triglycerides; D008071:Lipoprotein Lipase