Lipoprotein lipase gene variation is associated with a paternal history of premature coronary artery disease and fasting and postprandial plasma triglycerides: the European Atherosclerosis Research Study (EARS)

Arteriosclerosis, Thrombosis, and Vascular Biology
S HumphriesP J Talmud

Abstract

The H-allele of the intron 8 HindIII polymorphism in the lipoprotein lipase (LPL) gene has been associated with a lower risk of myocardial infarction (MI) and plasma levels of triglycerides (TG). To test whether the HindIII site was in linkage disequilibrium with the functional variant LPL Serine447Stop (S447X), subjects from the European Atherosclerosis Research Study (EARS I) were genotyped for both polymorphic sites. This study included 515 offspring of fathers with a premature (<55 years old) MI, who were designated cases, and 930 age- and sex-matched control subjects from five different regions of Europe. Linkage disequilibrium between the two sites was very strong (>.99), with only three of the four possible haplotypes identified: H+S447, H-S447, and H-X447. The frequency of the H-X447 but not of the H-S447 haplotype was significantly lower in cases than in control subjects (.090 versus .117, P<.01) suggesting a protective effect for MI, with this difference being consistent in all five regions of Europe. Compared with individuals homozygous for the H+S447 haplotype, the odds ratio of having a paternal history of premature MI for H-X447 heterozygotes (approximately 20% of the population) was 0.71 (95% confidence interval,...Continue Reading

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