Key result
APOA4-A5-ZNF259-BUD13 variants double high triglyceride risk without increasing coronary heart disease.
Why the study?
The role of genetic variants in the APOA4-APOA5-ZNF259-BUD13 gene cluster in influencing triglyceride levels and coronary heart disease risk in a Chinese population was unclear.
Do polymorphisms in the APOA4-APOA5-ZNF259-BUD13 gene cluster increase plasma triglyceride levels and the risk of coronary heart disease in a Chinese Han population?
Observational (n=8,099)
Do polymorphisms in the APOA4-APOA5-ZNF259-BUD13 gene cluster increase plasma triglyceride levels and the risk of coronary heart disease in a Chinese Han population?
Genetic variants in the APOA4-APOA5-ZNF259-BUD13 gene cluster are strongly associated with elevated triglyceride levels but not with increased CHD risk in the Chinese Han population.
Variants link APOA4-APOA5 cluster to TG levels but not CHD risk in Chinese adults; leaves causal pathways open for further study.
BACKGROUND/AIM: Recent genome-wide association studies have identified several loci influencing lipid levels. The present study focused on the triglycerides (TG)-associated locus, the APOA4-APOA5-ZNF259-BUD13 gene cluster on chromosome 11, to explore the role of genetic variants in this gene cluster in the development of increasing TG levels and coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: Six single nucleotide polymorphisms (SNPs), rs4417316, rs651821, rs6589566, rs7396835, rs964184 and rs17119975, in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped in 5374 healthy Chinese subjects. There were strong significant associations between the six SNPs and TG levels (P < 1.0 × 10(-8)). Moreover, a weighted genotype score was found to be associated with TG levels (P = 3.28 × 10(-13)). The frequencies of three common haplotypes were observed to be significantly different between the high TG group and the low TG group (P < 0.05). However, no significant effects were found for the SNPs regarding susceptibility to CHD in the Chinese case-control populations. CONCLUSIONS/SIGNIFICANCE: This study highlights the genotypes, genotype scores and haplotypes of the APOA4-APOA5-ZNF259-BUD13 gene cluster that were associated with TG levels in a Chinese population; however, the genetic variants in this gene cluster did not increase the risk of CHD in the Chinese population.
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Fu et al. (2015) conducted an observational in Hypertriglyceridemia and Coronary Heart Disease (n=8,099). Polymorphisms in APOA4-APOA5-ZNF259-BUD13 gene cluster vs. Reference genotypes / non-carriers was evaluated on High triglyceride levels (≥1.70 mmol/L) (OR 2.22, 95% CI 1.57-3.14, p=4.91×10^-6). Polymorphisms in the APOA4-APOA5-ZNF259-BUD13 gene cluster were strongly associated with elevated triglyceride levels (OR 2.22 for the TCACC haplotype), but did not increase the risk of coronary heart disease in a Chinese Han population.
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