on December 12, 2002
Published online before print December 12, 2002, doi: 10.1161/01.ATV.0000051406.14162.6A
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Submitted on November 20, 2002
Accepted on November 21, 2002
A Quantitative Trait Locus on Chromosome 16q Influences Variation in Plasma HDL-C Levels in Mexican Americans
M. C. Mahaney *;
From the Department of Genetics (M.C.M., L.A., D.L.R., J.L.V.d.B., S.A.C., J.B., J.W.M.), Southwest Foundation for Biomedical Research, San Antonio, and the Human Genetics Center (J.E.H.), School of Public Health, University of Texas Health Science Center at Houston, Tex.
* To whom correspondence should be addressed. E-mail: mmahaney{at}darwin.sfbr.org.
Objective—We conducted a whole-genome, multipoint linkage screen to localize a previously reported major locus accounting for 56% to 67% of the additive genetic effects on covariate-adjusted plasma HDL cholesterol (HDL-C) levels in Mexican Americans from the San Antonio Family Heart Study (SAFHS).
Methods and Results—After using complex segregation analysis to recover the major locus in 472 SAFHS participants from 10 genotyped families, we incorporated covariates required to detect that major locus, including plasma levels of triglycerides and apolipoprotein A-I, in a maximum-likelihood-based variance-components linkage screen. Only chromosome 16 exhibited convincing evidence for a quantitative trait locus (QTL), with a peak multipoint log of the odds (LOD)=3.73 (P=0.000034). Subsequent penetrance model-based linkage analysis, incorporating genotypes at the marker locus nearest the multipoint peak (D16S518) into the segregation model, detected linkage with the previously detected major locus (LOD=2.73, P=0.000642). Initial estimates place this QTL within a 15-cM region of chromosome 16q near the structural loci for lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP).
Conclusions—A QTL influencing plasma levels of HDL-C in Mexican Americans from San Antonio maps to a region of human chromosome 16q near LCAT and CETP.
Key words: HDL • genome screen • linkage • heritability • Mexican Americans
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