GLP1R基因变异和性别影响严重肥胖患者对西马鲁肽治疗的反应。

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2025-05-19 DOI:10.1002/oby.24300

Aurélie Phan, Claire Carette, Céline Narjoz, Claire Rives-Lange, Nathalie Rassy, Sebastien Czernichow, Nicolas Pallet

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引用次数: 0

摘要

目的：本研究的目的是确定胰高血糖素样肽-1受体（GLP1R）基因变异rs6923761G→A是否影响重度肥胖患者的半马鲁肽反应。方法：从2023年3月至2024年7月，我们前瞻性地对112例每周使用2.4 mg西马鲁肽的患者进行基因分型。所有患者均治疗3级肥胖（BMI≥40 kg/m2）超过4个月。结果：112例患者中rs6923761 AA变异频率为9例（8%），GA为42例（37.5%），GG为61例（54.5%）。变异A纯合子的平均体重减轻动力学为每月1.64% (SD 0.78%)，而至少一个G变异携带者的平均体重减轻动力学为每月1.04% (SD 0.79%) （p = 0.03）。多因素分析表明，rs6923761G→A和性别是体重减轻的独立预测因子。携带A等位基因的女性的体重减轻率是携带G等位基因的男性的两倍多：平均（SD）每月1.89%（0.75%）对0.7% (0.7%)（p = 0.0009）。A等位基因纯合的女性无一无应答，而携带G等位基因的男性有56%（37人中有21人）无应答。结论：rs6923761G→A基因变异和性别对重度肥胖患者服用西马鲁肽后体重减轻有深远影响。

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A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity

Objective

The objective of this study is to identify whether the glucagon-like peptide-1 receptor (GLP1R) gene variant rs6923761G→A has an influence on semaglutide response in individuals with severe obesity.

Methods

From March 2023 to July 2024, we prospectively genotyped 112 patients treated with semaglutide 2.4 mg weekly. All patients had been treated over 4 months for grade 3 obesity (BMI ≥ 40 kg/m²).

Results

The frequency of the rs6923761 AA variant was 9 out of 112 patients (8%), GA was 42 out of 112 (37.5%), and GG was 61 out of 112 (54.5%). The mean weight loss kinetics was 1.64% (SD 0.78%) per month in homozygotes of variant A in comparison with a mean weight loss of 1.04% (SD 0.79%) per month in carriers of at least one G variant (p = 0.03). Multivariate analysis demonstrated that rs6923761G→A and sex were independent predictors of weight loss. The rate of weight loss in women homozygous for the A allele was more than double that observed in men carrying the G allele: mean (SD) 1.89% (0.75%) per month versus 0.7% (0.7%) per month (p = 0.0009). No woman homozygous for the A allele was a nonresponder, compared with 56% (21 out of 37) of the men carrying the G allele.

Conclusions

The rs6923761G→A gene variant and sex profoundly affect weight loss in response to semaglutide in patients with severe obesity.

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.