Genome-wide search for QTLs for apolipoprotein A-I level in elderly Swedish DZ twins: evidence of female-specific locus on 15q11-13.
The effect of genetic variants underlying atherosclerosis is thought to be mediated through intermediate phenotypes such as serum cholesterol levels. Localization of quantitative trait loci influencing levels of serum lipids and (apo)lipoproteins may aid in the search for determinants of susceptibility to atherosclerotic diseases. Since apolipoprotein A-I is the primary protein constituent of high-density lipoprotein, it is considered to be critical for the antiatherogenic effect of high-density lipoproteins. We describe here an effort to map loci influencing apolipoprotein A-I levels. Measurements of apolipoprotein A-I levels and genome scans with more than 1000 microsatellite markers were successfully performed in both members of 501 pairs of fraternal twins from Sweden. Variance component linkage analysis was undertaken to map quantitative trait loci. In the total study sample, two loci showed comparable suggestive evidence of linkage, 6p21-12 (LOD=2.4) and 12q23 (LOD=2.4). Sex-limited analyses revealed significant female-specific linkage at marker D15S156 on 15q11-13 (LOD=4.1). The loci on 12q and 15q in the present study confirm previously reported loci for apolipoprotein A-I, while the peak on chromosome 6p lends further support to a locus influencing several phenotypes related to atherosclerosis. Intriguingly, the presence of genes belonging to the phospholipase A2 superfamily under three out of four observed linkage peaks would lend some support to the view that this group of genes might collectively represent candidates as apolipoprotein A-I level regulators.
Magnusson
Patrik K E
PK
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. patrik.magnusson@ki.se
Boman
Marcus
M
de Faire
Ulf
U
Perola
Markus
M
Peltonen
Leena
L
Pedersen
Nancy L
NL
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000097:blood* / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics*; D013548:Sweden; D014429:Twins, Dizygotic / Q000097:blood / Q000235:genetics*
D016632:Apolipoprotein A-I