| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Circulation | ||||
| Publisher: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 107 | ||||
| Number of Issue or Book Chapter: | 5 | ||||
| Page Range: | pp. 696-701 | ||||
| Date: | 2003 | ||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin II | ||||
| Identification Number: |
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| Keywords: | CORONARY-HEART-DISEASE; PENTANUCLEOTIDE REPEAT POLYMORPHISM; RISK-FACTORS; APO(A) GENE; ELEVATED LIPOPROTEIN(A); SEQUENCE POLYMORPHISMS; PLASMA LIPOPROTEIN(A); LP(A) CONCENTRATION; SIZE POLYMORPHISM; WOMEN; apolipoproteins; polymorphism; myocardial infarction; women; population | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 72415 |
Web of ScienceAbstract
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 ...
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 (less than or equal to8 PN 66.1 mg/dL versus >8 PN 8.7 mg/dL; P<0.0001). The odds to present with MI were elevated in individuals producing small Lp(a) particles (<= 22 K4 repeats; OR 1.47 for men and 1.69 for women; P<0.002) and in women with less than or equal to8 PN repeats (OR 1.46, P=0.009). Interestingly, in women, the frequent haplotype with less than or equal to8 PN and less than or equal to22 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 less than or equal to8 PN and less than or equal to22 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.
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