Association of branched chain amino acids related variant rs1440581 with risk of incident diabetes and longitudinal changes in insulin resistance in Chinese.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Polymorphism, Single Nucleotide*; Amino Acids, Branched-Chain/*blood ; Diabetes Mellitus, Type 2/*blood ; Diabetes Mellitus, Type 2/*genetics ; Insulin Resistance/*genetics ; Protein Phosphatase 2C/*genetics; Adult ; Aged ; Alleles ; Asian People/genetics ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Incidence ; Longitudinal Studies ; Male ; Middle Aged ; Weight Gain/genetics

Aims: 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.
Methods: 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.
Results: 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 Log 10 _FSI (β ± SE 0.027 ± 0.002) and Log 10 _HOMA-IR (0.030 ± 0.003), as compared to T-allele (both P for interaction = 0.003).
Conclusions: 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.

81471062 National Natural Science Foundation of China; 81471059 National Natural Science Foundation of China; 81500660 National Natural Science Foundation of China; 81561128019 National Natural Science Foundation of China; 2016YFC1305600 Ministry of Science and Technology of the People's Republic of China; 2016YFC1304904 Ministry of Science and Technology of the People's Republic of China; 2015DFA30560 National International Science Cooperation Foundation; 20152508 Gaofeng Clinical Medicine Grant Support from the Shanghai Municipal Education Commission; 20161301 Gaofeng Clinical Medicine Grant Support from the Shanghai Municipal Education Commission

Keywords: Branched chain amino acids; Genetic variant; Interaction; Longitudinal change; Type 2 diabetes

0 (Amino Acids, Branched-Chain)
EC 3.1.3.16 (PPM1K protein, human)
EC 3.1.3.16 (Protein Phosphatase 2C)

Date Created: 20180602 Date Completed: 20180927 Latest Revision: 20221207

20240628

10.1007/s00592-018-1165-4

29855804