Association of polymorphisms of the apolipoprotein(a) gene with lipoprotein(a) levels and myocardial infarction.
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.


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 (<or=8 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 (<or=22 K4 repeats; OR 1.47 for men and 1.69 for women; P<0.002) and in women with <or=8 PN repeats (OR 1.46, P=0.009). Interestingly, in women, the frequent haplotype with <or=8 PN and <or=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 <or=8 PN and <or=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.
Holmer
Stephan R
SR
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany. stephan.holmer@klinik.uni-regensburg.de
Hengstenberg
Christian
C
Kraft
Hans-Georg
HG
Mayer
Björn
B
Pöll
Melanie
M
Kürzinger
Susanne
S
Fischer
Marcus
M
Löwel
Hannelore
H
Klein
Gernot
G
Riegger
Günter A J
GA
Schunkert
Heribert
H
D001053:Apolipoproteins / Q000235:genetics*; D053241:Apoprotein(a); D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D018082:Kringles / Q000235:genetics; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012306:Risk
D001053:Apolipoproteins; D017270:Lipoprotein(a); D053241:Apoprotein(a)