Huang Tao, Zhuang Zhenhuang, Heianza Yoriko, Sun Dianjianyi, Ma Wenjie, Wang Wenxiu, Gao Meng, Fang Zhe, Ros Emilio, Del Gobbo Liana C, Salas-Salvadó Jordi, Martínez-González Miguel A, Polak Jan, Laakso Markku, Astrup Arne, Langin Dominique, Hager Jorg, Hul Gabby, Hansen Torben, Pedersen Oluf, Oppert Jean-Michel, Saris Wim H M, Arner Peter, Cofán Montserrat, Rajaram Sujatha, Tuomilehto Jaakko, Lindström Jaana, de Mello Vanessa D, Stancacova Alena, Uusitupa Matti, Svendstrup Mathilde, Sørensen Thorkild I A, Gardner Christopher D, Sabaté Joan, Corella Dolores, Martinez J Alfredo, Qi Lu
Department of Epidemiology & Biostatistics, School of Public Health, Peking University, China.
Department of Global Health, School of Public Health, Peking University, China.
Health Data Sci. 2021 Nov 3;2021:9897048. doi: 10.34133/2021/9897048. eCollection 2021.
. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs).. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies.. In the joint analysis, a total of 7 eligible RCTs were included (). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: , ; , ) per one copy of the T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of risk allele.. Our findings suggest that carrying the T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.
与2型糖尿病（T2D）相关的最强基因座是常见变异rs7903146所在的转录因子7样2基因。我们旨在通过多项随机对照试验（RCT），量化饮食/生活方式干预与rs7903146的基因效应在超重或肥胖成年人中对血糖性状、体重或腰围的相互作用。2016年10月至2018年5月，通过汇总7项RCT的个体参与者数据进行了一项大型合作分析。这些RCT报告了超重或肥胖成年人在饮食/生活方式相关干预后rs7903146变异体的血糖控制和肥胖情况变化。使用等位基因剂量编码的基因效应和常见协变量的基因-治疗相互作用模型适用于所有研究中的个体参与者数据。在联合分析中，共纳入了7项符合条件的RCT。重要的是，我们观察到饮食/生活方式相关干预对rs7903146变异体和空腹血糖变化有显著的效应修饰。与对照组相比，饮食/生活方式干预与每一个T风险等位基因拷贝使空腹血糖降低-3.06（95%CI，-5.77至-0.36）mg/dL（异质性检验和总体效应：，；，）相关。此外，无论遗传风险如何，饮食/生活方式干预与较低的腰围相关。然而，每一个风险等位基因拷贝在其他血糖控制和肥胖性状方面，饮食/生活方式干预没有显著变化。我们的研究结果表明，携带T风险等位基因可能对超重或肥胖成年人改善空腹血糖控制的特定饮食/生活方式干预有适度更大的益处。
