State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Acta Diabetol. 2018 Sep;55(9):901-908. doi: 10.1007/s00592-018-1165-4. Epub 2018 May 31.
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 Log_FSI (β ± SE 0.027 ± 0.002) and Log_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.
先前的全基因组关联研究表明，rs1440581 与欧洲人群循环支链氨基酸 (BCAA) 水平显著相关。我们旨在研究与 BCAA 相关的变异 rs1440581 与中国社区为基础的前瞻性队列中 2 型糖尿病 (T2D) 发病风险以及葡萄糖相关代谢特征的纵向变化之间的关联。
纳入了基线时年龄≥40 岁的来自社区人群的 6043 名非糖尿病参与者，并进行了 5 年的随访。对与 BCAA 相关的变异 rs1440581 进行了基因分型。T2D 的定义为空腹血糖 (FPG) ≥7.0mmol/L 或服用抗糖尿病药物。在基线和随访时评估了人体测量和生化测量。
在 5 年的随访期间，576 名（9.5%）参与者发生了 T2D。在调整混杂因素后，每个 C 等位基因与 T2D 发病风险增加 20%相关（优势比=1.20，95%置信区间[1.05，1.36]）。我们没有发现该变异对空腹血清胰岛素（FSI）水平或胰岛素抵抗（IR）的增加有主要影响。然而，我们发现 rs1440581 显著改变了体重增加对 FSI 和 HOMA-IR 增加的影响。在 C 等位基因携带者中，与 T 等位基因相比（交互作用 P 值均<0.003），体重指数增加与 FSI 的增加（β±SE 0.027±0.002）和 HOMA-IR 的增加（0.030±0.003）更为相关。
与 BCAA 相关的遗传变异 rs1440581 与中国人群中 T2D 的发病风险增加相关。该变异可能改变了体重增加对 IR 发展的影响。
