title: Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples.
abstract: 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.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7088, USA.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.forename: Laura
authors.initials: L
authors.lastname: Riba
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas-Vazquez
authors.forename: Maria L
authors.initials: ML
authors.lastname: Ordoñez-Sánchez
authors.forename: Rosario
authors.initials: R
authors.lastname: Rodriguez-Guillen
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Teresa
authors.initials: T
authors.lastname: Tusie-Luna
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
mesh_terms: 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*
chemical_list: D008076:Cholesterol, HDL; D014280:Triglycerides