Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.

Détails

ID Serval
serval:BIB_BFE17EB9D512
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.
Périodique
Annals of Human Genetics
Auteur(s)
Shah S.H., Kraus W.E., Crossman D.C., Granger C.B., Haines J.L., Jones C.J., Mooser V., Huang L., Haynes C., Dowdy E., Vega G.L., Grundy S.M., Vance J.M., Hauser E.R.
ISSN
0003-4800 (Print)
ISSN-L
0003-4800
Statut éditorial
Publié
Date de publication
2006
Volume
70
Numéro
Pt 6
Pages
738-748
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support
Résumé
Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease-related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results. We performed ordered subset analysis (OSA) and quantitative trait linkage (QTL) using serum lipoproteins and microsatellite markers in 346 families with early-onset CAD. OSA defined homogeneous subsets and calculated lod scores across a chromosome after ranking families by mean lipoprotein values. QTL used variance components analysis. We found significantly increased linkage to chromosome 3q13 (LOD 5.10, p = 0.008) in families with higher HDL cholesterol, lower LDL and total cholesterol, lower triglycerides, and fewer CAD risk factors, possibly due to a concentrated non-lipoprotein-related genetic effect. OSA identified linkage on chromosome 5q34 in families with higher cholesterol, possibly representing a hereditary lipoprotein phenotype. Multiple QTLs were identified, with the strongest for: total cholesterol on chromosome 5q14 (LOD 4.3); LDL on 20p12 (LOD 3.97); HDL on 3p14 (LOD 1.65); triglycerides on 18q22 (LOD 1.43); and HDL/TC ratio on 3q27-28 (LOD 2.06). Our findings suggest the presence of etiologic heterogeneity in families with early-onset CAD, potentially due to differential effects of lipoprotein phenotypes. Candidate genes are under investigation.
Mots-clé
Adult, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 5, Coronary Artery Disease/diagnosis, Coronary Artery Disease/genetics, Female, Genetic Linkage, Genetic Variation, Humans, Lipoproteins/blood, Lipoproteins/genetics, Lod Score, Male, Middle Aged, Phenotype, Quantitative Trait Loci
Pubmed
Web of science
Création de la notice
13/10/2013 22:08
Dernière modification de la notice
03/03/2018 21:04
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