rs174546

Meta-analysis of 34,748 European ancestry adults from 11 CHARGE Consortium cohorts examining sugar-sweetened beverage (SSB) intake associations with glycemic traits. SSB intake was associated with higher fasting glucose (β=0.014 mmol/l, p=1.5×10⁻³) and fasting insulin (β=0.030 log pmol/l, p=2.0×10⁻¹⁰). Although a suggestive interaction between SSB and KLB-rs1542423 was observed in discovery cohorts for fasting insulin (p=0.006), this was not confirmed in replication analysis.

A replication study in 21,004 Japanese and 1,203 Mongolian individuals demonstrated that rs174547 in FADS1/FADS2 is associated with plasma lipid profiles in Asian populations. In Japanese, the C allele was significantly associated with increased triglycerides (P=1.5×10⁻⁶, β=0.04 mg/dl per allele) and decreased HDL-C (P=0.03), while in Mongolians, the C allele was strongly associated with decreased LDL-C (P=2.6×10⁻⁶, β=-5.7 mg/dl per allele). The variable effects across populations despite similar genetic backgrounds suggest gene-environment interaction with dietary polyunsaturated fatty acid intake.