Association of mTOR genetic variants with anthropometric traits in Hong Kong Chinese with type 2 diabetes
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摘要Background: Obesity is a complex disease resulted from the interplay between genes and environment. mTOR pathway, a key neuronal regulator of energy homeostasis, is a potential target for therapeutic intervention in obesity. The hypothalamic nutrient-sensing networks integrate the hormonal (insulin, leptin, ghrelin) and nutritional signals to activate or suppress the mTOR signalling pathway3. Although genome-wide association studies (GWAS) have revealed 396 obesity-related loci to date, data in Asian type 2 diabetes populations are sparse.

Aim: We aimed to examine the association of mTOR genetic variants and anthropometric traits in Chinese with type 2 diabetes.

Methods: All registrants of Hong Kong Diabetes Registry were recruited from the year 1994 to 2007, underwent comprehensive diabetes assessment with available DNA after informed consents were sought. Samples were genotyped for mTOR locus using the Illumina Omni 2.5+ exome array. After standard quality control, a total of 5892 subjects and 35 genotyped single nucleotide polymorphisms (SNPs) with minor allele frequency ≥0.01 were included. Participants were categorized according to their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2), obesity (25.0-29.9 kg/m2), and extreme obesity (≥30.0 kg/m2). Central adiposity was defined as waist circumference (WC) ≥90 cm in male and ≥80 cm in female, whilst the corresponding waist-hip-ratio (WHR) were ≥0.90 and ≥0.85. Associations of SNPs with baseline anthropometric traits were explored in an additive model utilizing linear or logistic regression analyses as applicable and stratified by sex, adjusting for age, duration of diabetes, principal components of global ancestry, and BMI (as appropriate).

Results: At baseline, mean age (±standard deviation) was 57.5±12.9 years, 46.2% were male, mean BMI was 25.2±4.0 kg/m2, and median (interquartile range) duration of diabetes was 6 (2-11) years. Two variants, which were rs6685950 near UBIAD1 (OR 0.765, 95% CI 0.624-0.936, P=0.009) and rs12122605 near mTOR (OR 0.856, 95% CI 0.735-0.997, P=0.046) had significant associations with extreme obesity, compared to the BMI <30.0 kg/m2 group (N=584 versus 5125). When compared to the normal weight group, only rs6685950 was significantly associated with extreme obesity (OR 0.783, 95% CI 0.623-0.983, P=0.035; N=584 versus 1564). Stronger associations with central adiposity traits were observed in male subjects at rs12121605 near mTOR for WC adjusted for BMI (betamale = -0.263, betafemale =0.160, Psex-interaction =0.048) and rs11121691 near mTOR for WHR adjusted for BMI (betamale = 0.005, betafemale = -0.004, Psex-interaction =0.046). The opposing effect of rs6685950 near UBIAD1 on BMI with previous work could be attributed to ancestral heterogeneity and a higher effect of allele frequency in our cohort. Linear regression analysis of SNPs and BMI was not significant. There were no statistically significant associations between SNPs, WC and WHR (P≥0.050).

Conclusion: Significant nominal associations of three variants on mTOR locus with overall and central adiposity were identified in Chinese with type 2 diabetes. Sexual dimorphism was evident in waist-related traits.

Disclosures: The authors declare no potential conflicts of interest relevant to this work.

Grant/support information: This work was funded by the Theme-based Research Scheme supported by the Research Grants Council of Hong Kong and the Hong Kong Association for the Study of Obesity Research Grant.
出版社接受日期05.07.2017
著者Lee-Ling Lim, Katie K.H. Chan, Ronald C.W. Ma, Eric S.H. Lau, Claudia H.T. Tam, Guozhi Jiang, Heung-Man Lee, Cadmon K.P. Lim, Risa Ozaki, Andrea O.Y. Luk, Juliana C.N. Chan, Alice P.S. Kong
會議名稱International Diabetes Federation World Diabetes Congress 2017
會議開始日04.12.2017
會議完結日08.12.2017
會議地點Abu Dhabi
會議國家/地區阿拉伯聯合酋長國
出版年份2017
語言英式英語
關鍵詞genetic, obesity, Asian

上次更新時間 2018-13-06 於 09:49