TCF7L2 variation predicts hyperglycentia incidence in a French general population -: The Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study
TCF7L2 variation predicts hyperglycentia incidence in a French general population -: The Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study
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DOI：
10.2337/db06-0692
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发表时间：
2006-11-01
期刊：
影响因子：
7.7
通讯作者：
Froguel, Philippe
中科院分区：
文献类型：
--
作者：
Cauchi, Stephane;Meyre, David;Froguel, Philippe
最近，病例对照研究表明，TCF7L2（转录因子 7 样 2 基因）非编码变异（rs7903146 T 风险等位基因）与 2 型糖尿病风险增加密切相关。然而，该标记物在未经选择的一般人群中的预测价值仍然未知。在这项研究中，oar 的目的是在法国 DESIR（胰岛素抵抗综合征流行病学研究数据）队列中对 4,976 名中年参与者进行为期 9 年的前瞻性研究，评估该变异对高血糖（2 型糖尿病和空腹血糖受损）患病率和发生率以及胰岛素调节的影响。我们的数据支持之前的研究，即 T 风险等位基因与基线时高血糖发生率较高（P = 0.049）以及 9 年随访后高血糖发生率较高（P = 0.014）相关。在前瞻性研究结束时，由于 T 风险等位基因而导致高血糖的人群归因风险估计为 10.4%。最有可能的遗传模型被发现是可加的（P = 0.002）而不是偏离线性（P = 0.098）。在 9 年的随访期间，C/C、C/T 和 T/T 携带者的生存分析证实了高血糖发生率的增加（对数秩检验 P = 0.028）。有趣的是，在对照个体中，有微弱的证据表明 T 风险等位基因与对照个体中空腹胰岛素水平和胰岛素分泌指数（β 细胞功能的稳态模型评估）降低之间存在关联。我们得出的结论是，TCF7L2 T 风险等位基因变异 (rs7903146) 可预测法国普通人群的高血糖发生率，可能是通过对胰岛素分泌的有害影响来实现的。
Recently, case-control studies demonstrated that a TCF7L2 (transcription factor 7-like 2 gene) noncoding variant (rs7903146 T at-risk allele) was strongly associated with an increased risk of type 2 diabetes. However, the predictive value of this marker in a nonselected general population remains unknown. In this study, oar aim was to assess the contribution of this variant to the prevalence and incidence of hyperglycemia (type 2 diabetes and impaired fasting glucose) and insulin regulation in a 9-year prospective study of 4,976 middle-aged participants in the French DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) cohort. Our data support previous studies associating the T at-risk allele with a higher prevalence of hyperglycemia at baseline (P = 0.049) and a higher incidence of hyperglycemia after 9 years of follow-up (P = 0.014). The population-attributable risk to develop hyperglycemia due to the T at-risk allele was estimated to be 10.4% at the end of the prospective study. The most likely inheritance model was found to be additive (P = 0.002) rather than deviating from linearity (P = 0.098). An increase in the incidence of hyperglycemia was confirmed by survival analyses among C/C, C/T, and T/T carriers during the 9 years of follow-up (P = 0.028 by log-rank test). Interestingly, in control individuals, there was weak evidence of association of the T at-risk allele with reduced fasting insulin levels and insulin secretion index (homeostasis model assessment of beta-cell function) in control individuals. We conclude that the TCF7L2 T at-risk allele variation (rs7903146) predicts hyperglycemia incidence in a general French population, possibly through a deleterious effect on insulin secretion.