Evidence for a major quantitative trait locus on chromosome 17q21 affecting low-density lipoprotein peak particle diameter.
BACKGROUND
Several lines of evidence suggest that small dense LDL particles are associated with the risk of coronary heart disease. Heritability and segregation studies suggest that LDL particle size is characterized by a large genetic contribution and the presence of a putative major genetic locus. However, association and linkage analyses have thus far been inconclusive in identifying the underlying gene(s).


RESULTS
An autosomal genome-wide scan for LDL peak particle diameter (LDL-PPD) was performed in the Québec Family Study. A total of 442 markers were genotyped, with an average intermarker distance of 7.2 cM. LDL-PPD was measured by gradient gel electrophoresis in 681 subjects from 236 nuclear families. Linkage was tested by both sib-pair-based and variance components-based linkage methods. The strongest evidence of linkage was found on chromosome 17q21.33 at marker D17S1301, with an LOD score of 6.76 by the variance-components method for the phenotype adjusted for age, body mass index, and triglyceride levels. Similar results were obtained with the sib-pair method (P<0.0001). Other chromosomal regions harboring markers with highly suggestive evidence of linkage (P< or =0.0023; LOD > or =1.75) include 1p31, 2q33.2, 4p15.2, 5q12.3, and 14q31. Several candidate genes are localized under the peak linkages, including apolipoprotein H on chromosome 17q, the apolipoprotein E receptor 2, and members of the phospholipase A2 family on chromosome 1p as well as HMG-CoA reductase on chromosome 5q.


CONCLUSIONS
This genome-wide scan for LDL-PPD indicates the presence of a major quantitative trait locus located on chromosome 17q and others interesting loci influencing the phenotype.
Lipid Research Center, CHUL Research Center, Laval University, Sainte-Foy, Québec, G1V 4G2, Canada.
Yohan
Y
Bossé
Louis
L
Pérusse
Jean-Pierre
JP
Després
Benoît
B
Lamarche
Yvon C
YC
Chagnon
Treva
T
Rice
D C
DC
Rao
Claude
C
Bouchard
Marie-Claude
MC
Vohl
D000328:Adult; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D010641:Phenotype; D040641:Quantitative Trait Loci
D008077:Lipoproteins, LDL