Division of Endocrinology and Metabolism, Indiana University, Indianapolis, IN, USA.
Diabet Med. 2012 Dec;29(12):1579-88. doi: 10.1111/j.1464-5491.2012.03662.x.
Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population.
Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling.
Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations.
ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.
基础脂联素浓度可预测糖尿病预防计划中的 2 型糖尿病发病。我们检验了这样一个假设，即编码脂联素（ADIPOQ）及其受体（ADIPOR1、ADIPOR2）的基因中的常见变异与循环脂联素浓度以及/或糖尿病预防计划人群中的糖尿病发病率相关。
对 ADIPOQ（24 个）、ADIPOR1（22 个）和 ADIPOR2（31 个）中的 77 个标记单核苷酸多态性（SNP）进行基因分型。使用线性模型评估 SNP 与基线脂联素浓度的相关性。使用 Cox 比例风险模型评估 SNP 与糖尿病发病率的相关性。
24 个 ADIPOQ SNP 中有 13 个与基线脂联素浓度显著相关。包括这 13 个 SNP 的多变量分析显示，rs17366568、rs1648707、rs17373414 和 rs1403696 对脂联素浓度有很强的独立贡献。然而，没有 ADIPOQ SNP 与糖尿病发病率直接相关。两个 ADIPOR1 SNP（rs1342387 和 rs12733285）与携带次要等位基因的个体的糖尿病发病率增加约 18%有关，且在不同治疗组之间没有差异，与脂联素浓度也没有任何关系。
ADIPOQ SNP 与糖尿病预防计划队列中的脂联素浓度显著相关。这一观察结果将先前在欧洲血统的未选择人群中的观察结果扩展到更广泛的多种族人群中，并证实了这些变异在肥胖/糖血症人群中的相关性。尽管在该队列中脂联素浓度与糖尿病风险之间存在很强的相关性，但与脂联素浓度相关的 ADIPOQ 变异与该人群的糖尿病风险无关。ADIPOR1 变异对糖尿病风险的影响与脂联素浓度无关。
