Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples.
BACKGROUND
Although epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies for lipids.


RESULTS
We investigated 6 single-nucleotide polymorphisms associated with triglycerides, 7 with high-density lipoprotein cholesterol, and 1 with both triglycerides and high-density lipoprotein cholesterol in recent Caucasian genome-wide association studies in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genes ABCA1, ANGPTL3, APOA5, APOB, CETP, GALNT2, GCKR, LCAT, LIPC, LPL (2), MMAB-MVK, TRIB1, and XKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2298) using the Z method to combine statistics. Ten of the single-nucleotide polymorphisms were nominally significant and 5 were significant after Bonferroni correction (P=2.20 x 10(-3) to 2.6 x 10(-11)) for the number of tests performed (APOA5, CETP, GCKR, and GALNT2). Interestingly, our strongest signal was obtained for triglycerides with the minor allele of rs964184 (P=2.6 x 10(-11)) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in whites (12%).


CONCLUSIONS
It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of 5 Caucasian genome-wide association studies lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (odds ratio, 1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans.
Weissglas-Volkov
Daphna
D
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7088, USA.
Aguilar-Salinas
Carlos A
CA
Sinsheimer
Janet S
JS
Riba
Laura
L
Huertas-Vazquez
Adriana
A
Ordoñez-Sánchez
Maria L
ML
Rodriguez-Guillen
Rosario
R
Cantor
Rita M
RM
Tusie-Luna
Teresa
T
Pajukanta
Päivi
P
D000483:Alleles; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics*; D005190:Family; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics; D017058:Mexican Americans / Q000235:genetics; D008800:Mexico; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood / Q000235:genetics*; D044465:White People / Q000235:genetics*
D008076:Cholesterol, HDL; D014280:Triglycerides