Zhibin Li1,2, Mingzhu Lin3, Changqin Liu3,4, Zheng Chen3, Dongmei Wang5, Xiulin Shi3, Shuyu Yang1,3, Xue-Jun Li1,3. 1. Xiamen Diabetes Institute, The First Affiliated Hospital, Xiamen University, Xiamen, China. 2. Epidemiology Research Unit, The First Affiliated Hospital, Xiamen University, Xiamen, China. 3. Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China. 4. Department of Endocrinology and Diabetes, The Teaching Hospital of Fujian Medical University, Xiamen, China. 5. School of Medicine, Xiamen University, Xiamen, China.
Abstract
BACKGROUND: 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.
BACKGROUND: This study explored associations of genetic variants in the fetuin B (FETUB) locus with intrahepatictriglyceride (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 FETUBrs4686434 (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 PNPLA3rs738409 (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 FETUBrs4686434 (AG/GG vs AA, β -2.27 ± 0.91, P = 0.012), but was higher in carriers of the minor G allele for PNPLA3rs738409 (CG/GG vs CC, β 2.65 ± 0.97, P = 0.006). There was a significant joint effect between FETUBrs4686434 and PNPLA3rs738409 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 FETUBrs4686434 was significantly associated with decreased IHTG content and may affect hepatic triglyceride accumulation in individuals at high risk of non-alcoholic fatty liver disease.