亚洲严重肥胖儿童的新型梅拉诺科尔-3和-4受体功能变体
Siong Gim Ong1,2, Roghayeh Dehghan3,4, Rajkumar Dorajoo3
1Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
The Journal of clinical endocrinology and metabolism
|October 11, 2023
概括
黑色皮质素3受体 (MC3R) 和黑色皮质素4受体 (MC4R) 基因的遗传变异与儿童肥胖有关. 功能性测试揭示了两个变体,MC3R p.Glu43Lys和MC4R p.Met91Arg,可能会使个体易患早期肥胖.
科学领域:
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
- 肥胖问题研究研究
背景情况:
- MC3R和MC4R基因的遗传变异与儿童肥胖症有很强的关联.
- 了解这些遗传因素对于解决早发性肥胖的流行率上升至关重要.
研究的目的:
- 在亚洲儿童中识别和功能性描述MC3R和MC4R变异,这些儿童患有严重的早期肥胖症.
- 调查已识别的变种对细胞信号通路的影响.
主要方法:
- 在488名亚洲儿童中,采用全外组测序来选MC3R和MC4R编码变异.
- 功能性表征涉及测量细胞内循环腺单酸盐 (cAMP) 度和光酶活性.
主要成果:
- 检测到6种异构的非同义罕见变异 (4个MC3R,2个MC4R),包括3种新型变异.
- 在MC3R p.Glu43Lys和MC4R p.Met91Arg变异中显示出有缺陷的cAMP信号.
- MC4R p.Gln43Lys在低基质度下表现出降低的cAMP信号,在高度下恢复.
- 对于异合体变种,没有观察到主导的负面影响.
结论:
- MC3R p.Glu43Lys和MC4R p.Met91Arg变种可能会使个体易患早期肥胖.
- 需要进一步的研究来证实这些变体在肥胖病原性中的致病作用.
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