Association of genetic variation in the leptin-melanocortin system with drive for thinness in patients with eating disorders: A pilot study

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-02-25 DOI:10.1016/j.gene.2025.149364

Laura González-Rodríguez , Luz María González , Angustias García-Herráiz , Sonia Mota-Zamorano , Isalud Flores , Guillermo Gervasini

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Abstract

We aimed to investigate whether genetic variants in the leptin-melanocortin system involved in anorexigenic signaling influence personality dimensions and psychopathological symptoms in eating disorders (ED) patients. The population consisted of 309 ED patients [221 with anorexia nervosa (AN) and 88 with bulimia nervosa (BN)] and 396 healthy controls. Patients underwent psychometric assessment using the Eating Disorders Inventory Test-2 (EDI-2) and the Symptom Checklist 90 Revised (SCL-90R) questionnaires. Fourteen tag-SNPs in the LEP, POMC, and MC4R genes, were determined. Drive for thinness (DT) was significantly affected by genetic variability. After correction for multiple testing, regression models showed that AN patients carrying the LEP rs11761556 CC variant genotype scored higher in this scale than AA/CA carriers did [mean difference = 4.43 (2.18–6.68), p < 0.001], although the significance was restrained to the restrictive subtype [4.92 (2.00–7.83), p = 0.001]. BN patients with the LEP rs10954173 AA genotype displayed lower scores [-8.7 (−12.31--3.91); p < 0.001]. Finally, gene-gene interaction analyses revealed two SNP pairs associated with body-mass index in AN patients (LEPrs3828942-POMCrs1009388, p < 0.001 and LEP rs11763517-POMCrs1009388, p = 0.002). Regarding DT scores, the POMCrs6545975-LEP11763517 SNP pair showed the strongest effect (p < 0.001) in AN. Genetic variants in the leptin-melanocortin system, may interact to influence personality dimensions in ED patients, which highlights the importance of considering genetic factors in the pathophysiology of these disorders.

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瘦素-黑素皮质素系统遗传变异与饮食失调患者瘦化驱动的关联：一项初步研究

我们的目的是研究参与厌食信号的瘦素-黑素皮质素系统的遗传变异是否影响饮食失调（ED）患者的人格维度和精神病理症状。研究对象包括309例ED患者（神经性厌食症221例，神经性贪食症88例）和396名健康对照。采用进食障碍量表（edi2）和症状检查表（SCL-90R）问卷对患者进行心理测量。LEP、POMC和MC4R基因中的14个标签snp被确定。遗传变异显著影响瘦度驱动（DT）。经多重检验校正后，回归模型显示携带LEP rs11761556 CC变异基因型的AN患者在该量表中的得分高于AA/CA携带者[平均差异= 4.43 (2.18-6.68),p <；0.001]，但其显著性仅限于限制性亚型[4.92 (2.00-7.83),p = 0.001]。LEP rs10954173 AA基因型的BN患者得分较低[-8.7(- 12.31—3.91)；p & lt;0.001]。最后，基因-基因相互作用分析揭示了与AN患者体重指数相关的两个SNP对(LEPrs3828942-POMCrs1009388, p <；0.001和LEP rs11763517-POMCrs1009388， p = 0.002)。在DT评分方面，POMCrs6545975-LEP11763517 SNP对的影响最强(p <；0.001)。瘦素-黑素皮质素系统的遗传变异可能相互作用，影响ED患者的人格维度，这突出了在这些疾病的病理生理学中考虑遗传因素的重要性。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.