Association of Polymorphisms of the Apolipoprotein(a) Gene With Lipoprotein(a) Levels and Myocardial Infarction
- 11 February 2003
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 107 (5), 696-701
- https://doi.org/10.1161/01.cir.0000048125.79640.77
Abstract
Background— Serum lipoprotein(a) [Lp(a)] concentration is largely determined by variability at the apolipoprotein(a) gene locus. Most prominent effects relate to polymorphisms in the promoter (a pentanucleotide [PN] repeat) and coding regions (a kringle IV [K4] repeat), the latter of which also affects Lp(a) particle size. The impact of these polymorphisms on cardiovascular risk is poorly understood. Methods and Results— We studied both polymorphisms and Lp(a) levels in 834 registry-based myocardial infarction (MI) patients (38% women) and 1548 population-based controls. Lp(a) concentrations were inversely related with the numbers of K4 and PN repeats. However, the effect of the PN polymorphism was restricted to subjects producing small Lp(a) particles (≤8 PN 66.1 mg/dL versus >8 PN 8.7 mg/dL; P P < 0.002) and in women with ≤8 PN repeats (OR 1.46, P =0.009). Interestingly, in women, the frequent haplotype with ≤8 PN and ≤22 K4 repeats, which is related to high levels of small Lp(a) particles, resulted in an elevated OR for MI (1.79; P =0.01) independently of Lp(a) serum concentration. Conclusions— The K4 and PN repeat polymorphisms largely explain the high variability of serum Lp(a) levels. A haplotype with ≤8 PN and ≤22 K4 repeats is characterized by high concentrations of small Lp(a) particles. Our observation that this haplotype was associated with MI independently of Lp(a) serum levels may suggest that Lp(a) particle size in addition to its concentration may modulate MI risk in women.Keywords
This publication has 24 references indexed in Scilit:
- A comprehensive linkage analysis for myocardial infarction and its related risk factorsNature Genetics, 2002
- The importance of serum lipoprotein (a) as an independent risk factor for premature coronary artery disease in middle‐aged black and white women from the United StatesJournal of Internal Medicine, 1998
- Ten-year follow-up results from the Goettingen Risk, Incidence and Prevalence Study (GRIPS). I. Risk factors for myocardial infarction in a cohort of 5790 menAtherosclerosis, 1997
- Plasma lipoprotein(a) levels and expression of the apolipoprotein(a) gene are dependent on the nucleotide polymorphisms in its 5'-flanking region.JCI Insight, 1997
- Apolipoprotein(a) size and pentanucleotide repeat polymorphisms are associated with the degree of atherosclerosis in coronary heart diseaseAtherosclerosis, 1996
- Hypertriglyceridemia and elevated lipoprotein (a) are risk factors for major coronary events in middle-aged menThe American Journal of Cardiology, 1996
- Molecular definition of the extreme size polymorphism in apolipoprotein(a)Human Molecular Genetics, 1993
- Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.JCI Insight, 1992
- A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in womenAtherosclerosis, 1992
- Case finding, data quality aspects and comparability of myocardial infarction registers: Results of a south German register studyJournal of Clinical Epidemiology, 1991