Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 21, Issue 6, Pages 1106-1116Publisher
WILEY
DOI: 10.1111/jcmm.13042
Keywords
metabolic syndrome; genome-wide association study; single-nucleotide polymorphism; secondary signal; gene-environment interaction
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Funding
- National Key Technology R & D Program of China [2009BAI80B02, 2012BAI02B03]
- National Natural Science Foundation of China [81172755]
- 111 Project [B13026]
- Program for Zhejiang Leading Team of Science and Technology Innovation [2010R50050]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
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Metabolic syndrome (MetS), a cluster of metabolic disturbances that increase the risk for cardiovascular disease and diabetes, was because of genetic susceptibility and environmental risk factors. To identify the genetic variants associated with MetS and metabolic components, we conducted a genome-wide association study followed by replications in totally 12,720 participants from the north, north-eastern and eastern China. In combined analyses, independent of the top known signal at rs651821 on APOA5, we newly identified a secondary triglyceride-associated signal at rs180326 on BUD13 (P-combined = 2.4 x 10(-8)). Notably, by an integrated analysis of the genotypes and the serum levels of APOA5, BUD13 and triglyceride, we observed that BUD13 was another potential mediator, besides APOA5, of the association between rs651821 and serum triglyceride. rs671 (ALDH2), an east Asian-specific common variant, was found to be associated with MetS (P-combined = 9.7 x 10(-22)) in Han Chinese. The effects of rs671 on metabolic components were more prominent in drinkers than in non-drinkers. The replicated loci provided information on the genetic basis and mechanisms of MetS and metabolic components in Han Chinese.
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