Abstract
BackgroundNuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Emerging evidence from previous studies using animal models suggests that the NCOA3 gene (NCOA3) plays a critical role in lipid metabolism as well as adipogenesis and obesity. The present study aims to investigate the association between NCOA3 SNPs and dyslipidemia in the Chinese Han population.MethodsFive hundred and twenty-nine (529) Chinese Han subjects were recruited. Four tag SNPs (rs2425955G > T, rs6066394T > C, rs10485463C > G, and rs6094753G > A) in NCOA3, selected from the HapMap website, were genotyped using MALDI-TOF mass spectrometry. Data analysis was performed using SPSS 16.0, SNPStats and haploview 4.2.ResultsFour SNPs (rs2425955, rs6066394, rs10485463, and rs6094753) were associated with triglyceride levels. Except for SNP rs10485463, genotype distributions and allele frequencies of the other three NCOA3 SNPs (rs2425955, rs6066394, and rs6094753) were significantly different between hypertriglyceridemia subjects and normal group. Significant differences were also observed in allele frequencies and genotype distributions of SNP rs10485463 between low-HDL cholesterolemia subjects and normal group. Carriers of rs2425955 T allele had a lower risk of hypertriglyceridemia compared to GG genotype. Similar results were observed from rs6094753. Subjects with rs6066394 CT genotype had a lower risk of hypertriglyceridemia than those with the TT genotype; however, CC and TT genotypes showed no significant difference in the risk of hypertriglyceridemia. Similar results were found in the association between rs6066394 and hypercholesterolemia. The variant alleles of rs2425955, rs6066394 and rs6094753 were associated with a lower risk of hypertriglyceridemia compared with the wild-type alleles. The G allele of rs10485463 was associated with an increased risk of low-HDL cholesterolemia. In the log-additive model the association between rs2425955 and hypertriglyceridemia remained significant after Bonferroni correction, and genotypes with variant alleles were associated with a lower risk of hypertriglyceridemia.ConclusionsIn summary, this study demonstrated that variation in NCOA3 might influence the risk of dyslipidemia and serum lipid levels in Chinese Han population.
Highlights
Nuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes
Compared with the C allele of Single nucleotide polymorphism (SNP) rs10485463, the G allele of SNP rs10485463 was associated with low-HDL cholesterolemia (OR = 1.48, 95 % confidence intervals (CI) = 1.09–2.00)
Our data showed that four NCOA3 SNPs were associated with plasma levels of triglyceride, and except rs10485436, three other SNPs of NCOA3 gene were associated with a decreased risk of hypertriglyceridemia
Summary
Nuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Previous studies provided evidence that the NCOA3 gene (NCOA3) plays a primary role in adipogenesis as well as obesity by regulating the gene expression of peroxisome proliferator-activated receptor γ (PPARγ) - the master regulator of adipocyte development and differentiation [8,9,10,11,12,13,14,15,16]. These studies demonstrated that NCOA3 could enhance the transcriptional activity of PPARγ which promotes obesity, and that adipocyte differentiation was suppressed in NCOA3 knockout mice with a significantly decreased gene expression of PPARγ [8,9,10,11]. Studies revealed that obese people with VAT fat accumulation were more tightly related to the risk of suffering from diabetes mellitus and dyslipidemia than those with a normal fat distribution [18, 19]
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