Familial combined hyperlipidemia in Mexicans: association with upstream transcription factor 1 and linkage on chromosome 16q24.1.
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.


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.
Molecular y Medicina Genómica del Instituto de Investigaciones Biomédicas, UNAM, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico.
Adriana
A
Huertas-Vazquez
Carlos
C
Aguilar-Salinas
Aldons J
AJ
Lusis
Rita M
RM
Cantor
Samuel
S
Canizales-Quinteros
Jenny C
JC
Lee
Lizzette
L
Mariana-Nuñez
Roopa-Metha Laura
RM
Riba-Ramirez
Anne
A
Jokiaho
Teresa
T
Tusie-Luna
Päivi
P
Pajukanta
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000208:ethnology / Q000235:genetics; D002885:Chromosomes, Human, Pair 16; D005190:Family; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051720:Upstream Stimulatory Factors / Q000235:genetics*
C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors