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在 2 型糖尿病患者中,常见的褪黑素受体基因(MTNR1B)的 2 型糖尿病风险基因变异与死亡率之间没有关联。

No association between a common type 2 diabetes risk gene variant in the melatonin receptor gene (MTNR1B) and mortality among type 2 diabetes patients.

机构信息

Department of Surgical Sciences, Sleep Science Laboratory (BMC), Uppsala University, Uppsala, Sweden.

Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, Translational Neuroscience Center, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

出版信息

J Pineal Res. 2022 Mar;72(2):e12785. doi: 10.1111/jpi.12785. Epub 2022 Jan 8.

Abstract

The minor G risk allele in the common melatonin receptor gene (MTNR1B, rs10830963) has been associated with an increased risk of myocardial infarction among patients with type 2 diabetes (T2D). Furthermore, activating the melatonin receptor 1B through melatonin has been shown to promote cell proliferation, which could be hypothesized to increase cancer risk. Cardiovascular disease (CVD) and cancer are common causes of death among patients with T2D. Using data from 14 736  patients with T2D who participated in the UK Biobank investigation, we hypothesized an additive effect of the G risk allele on all-cause mortality, CVD mortality, and cancer mortality. As shown by Cox regression adjusted for confounders such as age, glucose-lowering medication, and socioeconomic status, no significant trend between the number of G risk alleles and mortality outcomes was found during the follow-up period of 11.1 years. Our negative findings do not speak against the role of this gene variant in the development of T2D, as repeatedly shown by previous large-scale studies. Instead, they may suggest that rs10830963 is less relevant for mortality risk in patients with T2D.

摘要

常见的褪黑素受体基因(MTNR1B,rs10830963)中的次要 G 风险等位基因与 2 型糖尿病(T2D)患者心肌梗死风险增加相关。此外,通过褪黑素激活褪黑素受体 1B 已被证明可促进细胞增殖,这可能被假设为增加癌症风险。心血管疾病(CVD)和癌症是 T2D 患者常见的死亡原因。利用来自参与英国生物库研究的 14736 名 T2D 患者的数据,我们假设 G 风险等位基因对全因死亡率、CVD 死亡率和癌症死亡率存在累加效应。正如 Cox 回归分析所表明的,在 11.1 年的随访期间,在调整了年龄、降糖药物和社会经济地位等混杂因素后,没有发现 G 风险等位基因数量与死亡率之间存在显著趋势。我们的阴性发现并不反对该基因变异在 T2D 发展中的作用,因为之前的大规模研究已经反复证明了这一点。相反,它们可能表明 rs10830963 与 T2D 患者的死亡率风险相关性较低。

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