Published online before print June 23, 2005, doi: 10.1161/01.ATV.0000175297.37214.a0
© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Familial Combined Hyperlipidemia in Mexicans
Association With Upstream Transcription Factor 1 and Linkage on Chromosome 16q24.1
From the Unidad de Biología (A.H.-V., S.C-Q., L.R.-R., T.T.-L.), Molecular y Medicina Genómica del Instituto de Investigaciones Biomédicas de la UNAM y del Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico; the Department of Human Genetics (A.H.-V., A.J.L., R.M.C., J.C.L., A.J., P.P.), David Geffen School of Medicine at UCLA, University of California, Los Angeles; and the Department of Endocrinology and Metabolism (C.A.-S., L.M.-N., R.M.), Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico City, Mexico.
Correspondence to Päivi Pajukanta, MD, PhD, Department of Human Genetics, David Geffen School of Medicine at UCLA, Gonda Center, Room 5309A, 695 Charles E. Young Drive South, Los Angeles, California 90095-7088. E-mail ppajukanta{at}mednet.ucla.edu
Objective— To investigate the largely unknown genetic component of the common lipid disorder, familial combined hyperlipidemia (FCHL) in Mexicans, we analyzed the upstream transcription factor 1 (USF1) gene that was recently associated with FCHL and high triglycerides (TG) in Finns. We also analyzed the Mexican FCHL families for 26 microsatellite markers residing in the seven chromosomal regions on 2p25.1, 9p23, 10q11.23, 11q13, 16q24.1, 19q13, and 21q21, previously linked to FCHL in Whites.
Methods and Results— We genotyped 314 individuals in 24 Mexican families for 13 SNPs spanning an 88-kb region, including USF1. The FCHL and TG traits showed significant evidence for association with 3 SNPs, hCV1459766, rs3737787, and rs2073658, and haplotype analyses further supported these findings (probability values of 0.05 to 0.0009 for SNPs and their haplotypes). Of these SNPs, hCV1459766 is located in the F11 receptor (F11R) gene, located next to USF1, making it difficult to exclude. Importantly, the association was restricted to a considerably smaller region than in the Finns (14 kb versus 46 kb), possibly because of a different underlying linkage disequilibrium structure. In addition, 1 of the 7 regions, 16q24.1, showed suggestive evidence for linkage (a lod score of 2.6) for total cholesterol in Mexicans.
Conclusions— This study, the first to extensively investigate the genetic component of the common FCHL disorder in Mexicans, provides independent evidence for the role of USF1 in FCHL in an outbred population and links the 16q24.1 region to an FCHL-component trait in Mexicans.
To investigate the genetic component of familial combined hyperlipidemia (FCHL) in Mexican FCHL families, we analyzed the upstream transcription factor 1 (USF1) gene and 7 chromosomal loci previously identified for FCHL. In Mexicans, USF1 was associated with FCHL and triglycerides, and a locus on 16q24.1 linked to total cholesterol.
Key Words: familial combined hyperlipidemia • USF1 gene • complex traits • Mexican population • coronary heart disease
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