低估的二次并发症的风险在致病性和葡萄糖升高的GCK变体携带者与2型糖尿病
Kelly M Schiabor Barrett1, Natalie Telis2, Lisa M McEwen2
1Helix, 101 S Ellsworth Ave Suite 350, San Mateo, CA, USA. kelly.barrett@helix.com.
Communications medicine
|November 20, 2024
概括
对于GCK变异的遗传查至关重要. 患有2型糖尿病 (T2D) 的携带者面临两倍的并发症风险,突出了在T2D预防和治疗中需要精准医学的需要.
科学领域:
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
- 代谢疾病 代谢疾病
背景情况:
- 葡萄糖酶 (GCK) 基因变异,包括GCK-成熟期发病的年轻人糖尿病 (GCK-MODY),可以导致HbA1c水平升高,往往超过2型糖尿病 (T2D) 诊断值.
- 尽管HbA1c升高,但GCK-MODY患者在历史上表现出治疗效率降低和令人惊的T2D并发症缺乏,这促使人们对更广泛的人群中的GCK变体载体状况进行调查.
- 了解GCK变种携带者的T2D相关并发症对于准确的诊断和管理至关重要.
研究的目的:
- 用既定的致病性标准和预测葡萄糖升高的功能证据,在人口层面确定GCK变异载体.
- 在大型队列中评估致病性和葡萄糖升高的GCK变体的流行率.
- 调查GCK变体,T2D诊断和T2D相关并发症的发展之间的关联.
主要方法:
- 利用ACMG/AMP标准和GCK变体解释的功能/统计证据来预测血糖升高效应.
- 在两个大队伍中评估了GCK变异的存在,总数约为535,000个人.
- 进行了回顾性分析,以比较GCK变体携带者和非携带者之间的T2D诊断率和并发症发展.
主要成果:
- 鉴定了442名GCK变体的个体 (约1在1200人中),预计会增加葡萄糖,其中150人 (34%) 具有致病性解释.
- 与非携带者相比,GCK变体携带者接受T2D诊断的可能性要高得多:致病变体的10倍,其他葡萄糖升高变体的3倍.
- 与T2D患有致病性或葡萄糖升高GCK变异的携带者,与T2D患有非GCK个体相比,T2D相关并发症的发生率是T2D的两倍多.
结论:
- 人口级数据证实,GCK变体和T2D的个体中二次并发症增加.
- 对于致病性和葡萄糖升高的GCK变体的基因型定型应该被视为T2D精准医学策略的一部分.
- 这种方法可以帮助量身定制的治疗和预防T2D及其相关并发症.
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