mTOR pathway regulates energy homeostasis by integrating the hormonal and nutritional signals.1-3 Besides discordant results on the inter-relationship between obesity and menopause4, genetic data in Asian type 2 diabetes (T2D) populations are sparse. We aimed to examine the association of mTOR variants and anthropometric traits in postmenopausal Chinese with T2D.
A total of 3168 Chinese women from Hong Kong Diabetes Registry recruited between 1994-2007 were genotyped for mTOR locus using the Illumina Omni 2.5+ exome array. 35 genotyped single nucleotide polymorphisms (SNPs) with minor allele frequency ≥0.01 were included. Associations of SNPs with baseline body mass index (BMI), waist circumference (WC) and waist-hip-ratio (WHR) were explored in an additive model, stratified by age with a cut-off at 50 years (age of menopause), adjusting for age, T2D duration and principal components of global ancestry.
Mean age (±standard deviation) of the study cohort was 57.5±13.2 years. Median (inter-quartile range) T2D duration was 6 (2-12) years. Mean BMI and WC were 25.2±4.1 kg/m2 and 83.5±9.9 cm, respectively. For rs4845988 near mTOR, postmenopausal women (age ≥50 years) had significantly higher WC (betaWC 0.699, P=0.037) and WHR (betaWHR 0.005, P=0.019) than women aged <50 years (betaWC -1.114, P=0.050, Page-interaction=0.001, N=2165 vs 950; betaWHR -0.009, P=0.005, Page-interaction<0.001, N=2070 vs 878). They tended to have higher BMI (betaBMI 0.209, P=0.126 vs betaBMI -0.297, P=0.214 for women aged <50 years, Page-interaction=0.026, N=2204 vs 964). For rs2273335 near EXOSC10, postmenopausal women had significantly lower WC (betaWC -1.030, P=0.006) and BMI (betaBMI -0.350, P=0.023) than women aged <50 years (betaWC 0.559, P=0.388, Page-interaction=0.001; betaBMI 0.335, P=0.217, Page-interaction=0.002). For rs2076658 near mTOR, lower WC (betaWC -1.093, P=0.027) was seen in postmenopausal women than those aged <50 years (betaWC 0.630, P=0.434, Page-interaction=0.007).
Three variants on mTOR locus demonstrated significant age-specific effects with overall and central adiposity in Chinese women with T2D.