Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples

Circ Cardiovasc Genet. 2010 Feb;3(1):31-8. doi: 10.1161/CIRCGENETICS.109.908004. Epub 2009 Dec 11.


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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / genetics*
  • Dyslipidemias / genetics*
  • Family
  • Gene Frequency
  • Genetic Variation
  • Genetics, Population
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Hypertriglyceridemia / genetics
  • Mexican Americans / genetics
  • Mexico
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Triglycerides / blood
  • Triglycerides / genetics*
  • White People / genetics*


  • Cholesterol, HDL
  • Triglycerides