Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease

Abstract

Our goal was to further define the role of LPL gene polymorphisms in coronary heart disease (CHD) risk. We determined the frequencies of three LPL polymorphisms (D9N, N291S, and S447X) in 899 men from the Veterans Affairs HDL Intervention Trial (VA-HIT), a study that examined the potential benefits of increasing HDL with gemfibrozil in men with established CHD and low high density lipoprotein cholesterol (HDL-C; р 40 mg/dl), and compared them with those of men without CHD from the Framingham Offspring Study (FOS). In VA-HIT, genotype frequencies for LPL D9N, N291S, and S447X were 5.3, 4.5, and 13.0%, respectively. These values differed from those for men in FOS having an HDL-C of Ͼ 40, who had corresponding values of 3.2% ( P ‫؍‬ 0.06), 1.5% ( P Ͻ 0.01), and 18.2% ( P Ͻ 0.01). On gemfibrozil, carriers of the LPL N9 allele in VA-HIT had lower levels of large LDL ( ؊ 32%; P Ͻ 0.01) but higher levels of small, dense LDL ( ؉ 59%; P Ͻ 0.003) than did noncarriers. Consequently, mean LDL particle diameter was smaller in LPL N9 carriers than in noncarriers (20.14 ؎ 0.87 vs. 20.63 ؎ 0.80 nm; P Ͻ 0.003). In men with low HDL-C and CHD: 1 ) the LPL N9 and S291 alleles are more frequent than in CHD-free men with normal HDL-C, whereas the X447 allele is less frequent, and 2 ) the LPL N9 allele is associated with the LDL subclass response to gemfibrozil. -Brousseau,

Study of Common Genetic Variant S447X in Lipoprotein Lipase and Its Association with Lipids and Lipoproteins in Type 2 Diabetic Patients

“…One of the study of S447X variant in a general population showed the allele frequencies of 0.875 and 0.125 for 'S' and 'X' respectively [30]. These findings are similar to that of the present study, while in another study 'X' allele frequency was found to be 0.06, with a carrier frequency of 13 % in men with low-HDL-C level and with CHD [31].…”

“…A significant increase only in HDL-C was observed by Fujiwara et al [30] in carriers than wild type for LPL S447X variant in Mima general population. Brousseau et al [31] found no significant difference in TC, HDL-C, LDL-C and TG in carriers than wild type for this variant in men with low HDL-C level and with CHD.…”

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

“…In association studies, although the X447 allele has been reported to be associated with a favorable lipid profile in some studies [7][8]22] the results have not been confirmed in other studies [15]. Similarly, the association of the S447X polymorphism with CAD is inconsistent [10][11][12][13][14][15][16][17][18]. In a meta analysis the association of the S447X polymorphism with TG/HDL-C and CAD was found to be small compared to three other LPL amino acid polymorphisms examined [23] or it was gender-specific [24].…”

“…Several common LPL genetic variants have been widely studied, and among them HindIII in intron 8 (T→G at position 481), and S447X in exon 9 are of particular interest because of their common occurrence (25% and 9% of the less common alleles, respectively in most populations) and their associations with plasma lipid profile [6][7][8][9][10][11] and susceptibility to CAD [10][11][12][13][14][15] in several studies, although some inconsistent results have also been reported [16][17][18]. Since the HindIII polymorphism is located in the middle of intron 8, it is not considered to be functional but rather in linkage disequilibrium with a putative functional variant.…”

Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease

“…However, Hallman et al (10) did not find any association between the HindIII(-) allele and higher LPL activity. The associations of certain polymorphic loci in the LPL promoter, introns or exons with lipid disorders and coronary artery disease (CAD) have been reported by some groups (rs285, rs1800590, rs320, rs268, rs1801177) (6)(7)(8)(11)(12)(13)(14) but contested by other authors (15)(16)(17). To the best of our knowledge, no data on the screening of such specific polymorphisms in the Saudi population have been reported.…”