Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population

Abstract

Background/AimRecent 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 FindingsSix 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/SignificanceThis 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.

Effects of polymorphisms in APOA5 on the plasma levels of triglycerides and risk of coronary heart disease in Jilin, northeast China: a case–control study

“…Our results are not consistent with the results of previous studies that have supported the hypothesis that rs651821 is not significantly associated with CAD risk in a Chinese population. 25–27 This discrepancy might be explained by the fact that our study was a case–control study, and the cases were limited to survivors of CAD. This difference would certainly affect the full influence of the examined polymorphisms.…”

Association and interaction of APOA5, BUD13, CETP, LIPA and health-related behavior with metabolic syndrome in a Taiwanese population

“…Previously, the CETP gene has been reported in association with HDL levels in Caucasian212526 and Asian Indian25 subjects as well as with higher triglyceride levels in Caucasian subjects21. Additionally, BUD13 variants have been associated with triglyceride levels2728, total cholesterol levels27, and hypercholesterolaemia29 in Chinese subjects.…”

A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys

“…In this report, we describe a novel autosomal recessive disorder associated with biallelic ZPR1 mutations. This multisystem syndrome was the ZPR1 polymorphism rs964184C>G is associated with increased plasma triglyceride levels, [25][26][27] increased LDL cholesterol and decreased HDL cholesterol, 28 and increased risk of developing metabolic syndrome, although the precise molecular mechanism is unknown. 29,30 ZPR1 is a highly conserved protein with 2 ZnF motifs and 2 larger modular domains ( Figure 3A).…”