The rs4686434 variant in the fetuin B (FETUB) locus is associated with intrahepatic triglyceride content in obese Chinese adults.

This study explored associations of genetic variants in the fetuin B (FETUB) locus with intrahepatic triglyceride (IHTG) content. 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. 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). 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.