Published in the Arteriosclerosis, Thrombosis, and Vascular Biology, in September 2005; 25:1985-1991, and at the website of the Arteriosclerosis, Thrombosis, and Vascular Biology in June, 2005 (http://atvb.ahajournals.org/):
Familial Combined Hyperlipidemia in Mexicans
Association with Upstream Transcription Factor 1 and Linkage on Chromosome 16q24.1
Adriana Huertas-Vazquez1,2, Carlos Aguilar-Salinas3, Aldons J. Lusis2, Rita M. Cantor2, Samuel Canizales-Quinteros1, Jenny C. Lee2, Lizzette Mariana-Nuñez3, Roopa-Metha3, Laura Riba-Ramirez1, Anne Jokiaho2, Teresa Tusie-Luna1 and Päivi Pajukanta2
1Unidad de Biología 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
2Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California
3Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico City, Mexico
Correspondence should be addressed to:
Päivi Pajukanta, MD, PhD Assistant Professor 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, USA Phone: 1-310-267-2011, Fax: 1-310-794-5446 Email: firstname.lastname@example.org
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005; 25:1985-1991:
Conclusions: This study, 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.
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.
For further information, please contact:
Päivi Pajukanta, MD, PhD Assistant Professor
Adriana Huertas-Vazquez Ph.D. Student
The following data files can be downloaded: