Association of branched chain amino acids related variant rs1440581 with risk of incident diabetes and longitudinal changes in insulin resistance in Chinese
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Previous genome-wide association studies reported rs1440581 was significantly associated with circulating branched chain amino acids (BCAAs) levels in Europeans. We aimed to investigate association of BCAAs related variant rs1440581 with incident T2D risk and longitudinal changes in glucose-related metabolic traits in a community-based prospective cohort of Chinese.
6043 non-diabetic participants aged ≥ 40 years from a community-based population at baseline were included and followed-up for 5 years. The BCAAs related variant rs1440581 was genotyped. Incident T2D was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L or taking anti-diabetic therapy. Anthropometry and biochemical measurements were evaluated at both baseline and follow-up.
576 (9.5%) participants developed T2D during the 5-year follow-up. Each C-allele was associated with a 20% higher risk of incident T2D (odds ratio = 1.20, 95% confidence interval [1.05, 1.36]) after adjustments for the confounders. We did not find a main effect of the variant on increase in fasting serum insulin (FSI) level or insulin resistance (IR). However, we found rs1440581 significantly modified effect of weight gain on increase in FSI and HOMA-IR. In the C-allele carriers, body mass index increase was associated with greater increase in Log10_FSI (β ± SE 0.027 ± 0.002) and Log10_HOMA-IR (0.030 ± 0.003), as compared to T-allele (both P for interaction = 0.003).
BCAAs related genetic variant rs1440581 was associated with an increased risk of incident T2D in a Chinese population. This variant might modify effect of weight gain on development in IR.
KeywordsBranched chain amino acids Genetic variant Longitudinal change Interaction Type 2 diabetes
We thank all the study participants for their participation and contribution. We are also grateful for research team who contributed to data collection and laboratory measurement.
LX and YH performed/supervised genetic analyses, contributed to data interpretation, and wrote the manuscript; LX, YH, TW, ML, ZZ, JL, YX, and YC contributed to acquisition of clinical and genetic data and reviewed the manuscript; LX, YH, MX, YB, LQ and WW contributed to genetic analyses and data interpretation, and reviewed the manuscript; MX designed study, contributed to data interpretation, wrote the manuscript and takes full responsibility for the work as a whole.
This work was supported by grants from the National Natural Science Foundation of China (81471062, 81471059, 81500660 and 81500610), the Ministry of Science and Technology of China (2016YFC1305600 and 2016YFC1304904), Shanghai Jiao Tong University SMC-Chen Xing Project (2016), the Gaofeng Clinical Medicine Grant Support from the Shanghai Municipal Education Commission (20152508 and 20161301) and the Shanghai Pujiang Program (18PJ1409600).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study protocol was approved by the Institutional Review Board of Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.
Informed consent was obtained from all individual participants included in this study.
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