Genetic determinants of major blood lipids in Pakistanis compared with Europeans

Circ Cardiovasc Genet. 2010 Aug;3(4):348-57. doi: 10.1161/CIRCGENETICS.109.906180. Epub 2010 Jun 22.

Abstract

Background: Evidence is sparse about the genetic determinants of major lipids in Pakistanis.

Methods and results: Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)).

Conclusions: Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Europe
  • Female
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Lipid Metabolism / genetics*
  • Lipid Metabolism Disorders / blood
  • Lipid Metabolism Disorders / ethnology
  • Lipid Metabolism Disorders / genetics
  • Lipids / blood*
  • Lipids / genetics
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Pakistan
  • Polymorphism, Single Nucleotide

Substances

  • Lipids