Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.

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Morabia A, Cayanis E, Costanza MC, Ross BM, Flaherty MS, Alvin GB, Das K, Gilliam TC

Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.

Hum Mol Genet. 2003 Nov 1;12(21):2733-43. Epub 2003 Sep 9.

PubMed ID
12966036 [ View in PubMed
]
Abstract

This study explored the genetic basis of the combination of extreme blood levels of HDL-C and LDL-C, a well-studied endophenotype for CVD, which has several attractive features as a target for genetic analysis: (1) the trait is moderately heritable; (2) non-genetic risk factors account for a significant but still limited portion of the phenotypic variance; (3) it is known to be moderated by a number of gene products. We exhaustively surveyed 11 candidate genes for allelic variation in a random population-based sample characterized for known CVD risk factors and blood lipid profiles. With the goal of generating specific etiological hypotheses, we compared two groups of subjects with extreme lipid phenotypes, from the same source population, using a case-control design. Cases (n=186) were subjects, within the total sample of 1708 people, who scored in the upper tertile of LDL-C and the lowest tertile of HDL-C, while controls (n=185) scored in the lowest tertile of LDL-C and the upper tertile of HDL-C. We used logistic regression and a four-tiered, systematic model building strategy with internal cross-validation and bootstrapping to investigate the relationships between the trait and 275 genetic variants in the presence of 10 non-genetic risk factors. Our results implicate a subset of nine genetic variants, spanning seven candidate genes, together with five environmental risk factors, in the etiology of extreme lipoprotein phenotypes. We propose a model involving these 14 genetic and non-genetic risk factors for evaluation in future independent studies.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
ATP-binding cassette sub-family A member 1O95477Details
Scavenger receptor class B member 1Q8WTV0Details
Lipoprotein lipaseP06858Details
Apolipoprotein EP02649Details
Apolipoprotein A-IP02647Details
Cholesteryl ester transfer proteinP11597Details
Phospholipid transfer proteinP55058Details