The KSR2-rs7973260 Polymorphism is Associated with Metabolic Phenotypes, but Not Psychological Phenotypes, in Chinese...

To examine the associations between genetic variants of KSR2 (kinase suppressor of RAS)-rs7973260, RAPGEF6 (guanine nucleotide exchange factor 6)-rs3756290, LOC105377703-rs4481363, and subjective well-being (SWB) and depressive symptoms (DSs) in Chinese elders, which were recently associated in a genome-wide association study conducted in Caucasians. The pleiotropic effects of KSR2-rs7973260 on metabolic phenotypes were also explored.

We used data from 1788 older individuals aged 70-84 years from the aging arm of the Rugao Longevity and Aging Study, a population-based cohort study conducted in the Jiangsu province of China.

No significant distributions of genotype frequencies were observed between life-satisfied and -unsatisfied groups across those with the three polymorphisms. The level of SWB components (positive affect, negative affect, and affect balance) and DSs did not differ among genotypes of the three variants. However, the presence of GA+AA of KSR2-rs7973260 was significantly higher in the metabolic syndrome (MetS), severe hypertriglyceridemia (HTG), and diabetes groups than in control groups (43.7% vs. 37.6%, 46.4% vs. 37.6%, 45.8% vs. 37.9%, respectively). The A allele of rs7973260 was associated with increased risk of MetS, severe HTG, and diabetes with an odds ratios (95% confidence intervals) of 1.289 (1.002-1.658), 1.438 (1.076-1.921), and 1.384 (1.022-1.875), which remained significant after multiple adjustments.

Rs7973260, rs3756290, and rs4481363 were not associated with SWB and DSs in Chinese elders. However, the KSR2-rs7973260 A allele exhibited pleiotropic effects on some metabolic phenotypes in Chinese elders. These effects should be validated in future studies.