The rs4686434 variant in the fetuin B (FETUB) locus is associated with intrahepatic triglyceride content in obese Chinese adults
中国肥胖成年人FETUB基因 rs4686434遗传变异与肝内甘油三酯含量的关联性研究
Abstract
enBackground
This study explored associations of genetic variants in the fetuin B (FETUB) locus with intrahepatic triglyceride (IHTG) content.
Methods
Four tagging single-nucleotide polymorphisms (SNPs) of the FETUB locus and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 and transmembrane 6 super family member 2 (TM6SF2) rs58542926 were genotyped in 418 obese Chinese adults in whom serum FETUB and IHTG were measured.
Results
Subjects carrying the minor G allele for FETUB rs4686434 (AG/GG) had lower serum FETUB levels (mean [±SD] 3.89 ± 1.36 vs 4.22 ± 1.46 μg/mL; P = 0.021) and IHTG content (12.7 ± 9.4% vs 14.6 ± 9.8%; P = 0.045) than their controls (AA), whereas IHTG content was higher in those carrying the minor G allele for PNPLA3 rs738409 (CG/GG) than in their controls (CC; 14.5 ± 10.1% vs 12.0 ± 8.6%; P = 0.012). After adjusting for potential confounders, IHTG content was lower in carriers of the minor G allele for FETUB rs4686434 (AG/GG vs AA, β −2.27 ± 0.91, P = 0.012), but was higher in carriers of the minor G allele for PNPLA3 rs738409 (CG/GG vs CC, β 2.65 ± 0.97, P = 0.006). There was a significant joint effect between FETUB rs4686434 and PNPLA3 rs738409 on IHTG content, with increasing genetic risk score (counting the risk allele of A in rs4686434 and G in rs738409) being associated with higher IHTG content (β 1.85 ± 0.48, P <0.001).
Conclusions
Carrying the minor G allele for FETUB rs4686434 was significantly associated with decreased IHTG content and may affect hepatic triglyceride accumulation in individuals at high risk of non-alcoholic fatty liver disease.
Abstract
zh摘要
背景
本研究旨在探索FETUB基因的遗传变异与肝内甘油三酯(intrahepatic triglyceride, IHTG)含量的关系。
方法
本研究纳入418名肥胖的中国成年人, 检测其血清FETUB水平及IHTG的含量, 同时对FETUB基因的4个标签单核苷酸多态性(SNPs)以及PNPLA3基因rs738409和TM6SF2基因rs58542926进行基因型分析。
结果
与对照组的A等位基因携带者相比, FETUB rs4686434(AG/GG)的G等位基因携带者血清FETUB水平(AG/GG v.s. AA, 3.89 ± 1.36 v.s. 4.22 ± 1.46 μg/mL, P = 0.021)及IHTG含量(12.7% ± 9.4% v.s. 14.6% ± 9.8%, P = 0.045)均显著下降;而PNPLA3 rs738409(CG/GG)的G等位基因携带者的IHTG含量与对照组的C等位基因携带者相比显著增加(CG/GG v.s. CC, 14.5% ± 10.1% v.s. 12.0% ± 8.6%, P = 0.012)。校正可能的混杂因素后, 与对照组相比, FETUB rs4686434 G等位基因携带者的IHTG含量显著减少(AG/GG v.s. AA;β -2.27 ± 0.91, P= 0.012);而PNPLA3 rs738409 G等位基因携带者与对照组相比IHTG含量显著增加(CG/GG v.s. C, β 2.65 ± 0.97, P = 0.006)。另外, 本研究发现FETUB rs4686434与PNPLA3 rs738409对IHTG含量具有显著的联合作用, 随着遗传风险评分(计数rs4686434 A等位基因和rs738409 G等位基因个数总和)的升高, IHTG含量显著增加(β 1.85 ± 0.48, P < 0.001)。
结论
FETUB rs4686434 G等位基因可显著降低IHTG含量, 并可能影响非酒精性脂肪肝高危人群的肝脏甘油三酯聚积。
