Sex-specific impact of rs1260326 polymorphism on metabolic traits in an older Japanese population: the Bunkyo Health Study

Abstract

Background: Metabolic syndrome involves health problems influenced by aging and genetics. The glucokinase regulatory protein ( GCKR ) rs1260326 polymorphism (Leu446) is associated with metabolic traits. This study explores the impact of the GCKR rs1260326 polymorphism on metabolic traits in older Japanese with focusing on sex-specific differences. Methods: This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, examined 883 participants aged 65–84 years. Participants were excluded with diabetes, or on drug treatment for diabetes or dyslipidemia. The GCKR P446L polymorphism was analyzed and compared their characteristics of physical activity, dietary intake, body composition, and metabolic parameters. Results: Study participants with GCKR rs1260326 genotypes (C/C 20.7%, C/T 47.6%, T/T 31.7%) had a median age of 72 years, and 60.4% were women. Men with the T/T genotype, as compared to the C/C genotype, had a lower body weight, body mass index (BMI), and skeletal mass index. This genotype also associated with lower fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), and higher Matsuda index, but not after adjustment for age, BMI, and physical activity. In contrast, women with the T/T genotype, compared to the C/C genotype, showed higher C-reactive protein, fibroblast growth factor 21, and Matsuda index. They also had lower fasting insulin, insulin area under the curve, and HOMA-IR; with these associations being independent of age, BMI, and physical activity. Conclusion: The GCKR rs1260326 genotype-affected metabolic traits differentially by sex in older Japanese. This highlights the need to consider sex differences in GCKR -related metabolic outcomes.