Genetic Variations in AMPK, FOXO3A, and POMC Increase the Risk of Extreme Obesity.

IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM Journal of Obesity Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.1155/2024/3813621
Cinthia Vila Nova Santana, Luiz Alexandre Viana Magno, Adauto Versiani Ramos, Maria Angélica Rios, Valéria Cristina Sandrim, Luiz Armando De Marco, Débora Marques de Miranda, Marco Aurélio Romano-Silva
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Abstract

Objective: Genetic variability significantly impacts metabolism, weight gain, and feeding behaviors, predisposing individuals to obesity. This study explored how variations in key genes related to obesity-FOXO3A (forkhead box O3), AMPK (protein kinase AMP-activated), and POMC (proopiomelanocortin)-are associated with extreme obesity (EOB). Methods: We conducted a case-control study with 251 EOB patients and 212 healthy controls with a body mass index (BMI) of less than 25 kg/m2. We genotyped 10 single nucleotide variants (SNVs) using TaqMan-based assays. Results: Four SNVs-rs1536057 in FOXO3A, rs103685 in AMPK, rs934778, and rs6545975 in POMC-were associated with an increased risk of EOB. The strongest association was observed with rs934778 (POMC), which had a maximum odds ratio (OR) of 5.26 (95% CI: 2.86-9.09). While these genetic variations are closely linked to EOB, they do not affect serum glucose, triglycerides, HDL, LDL, BMI, or waist circumference. Conclusions: These findings indicate that factors beyond traditional metabolic pathways, potentially related to feeding behavior or hormonal regulation, may also link these genetic variations to obesity. Further research in a larger sample is essential to validate these findings and explore their potential to guide clinical interventions and public health strategies.

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AMPK、FOXO3A 和 POMC 的基因变异会增加极度肥胖的风险。
目的基因变异对新陈代谢、体重增加和进食行为有重大影响,易导致肥胖。本研究探讨了与肥胖有关的关键基因--FOXO3A(叉头盒 O3)、AMPK(蛋白激酶 AMP-活化)和 POMC(原髓皮质素)的变异如何与极度肥胖(EOB)相关。研究方法我们对 251 名 EOB 患者和 212 名体重指数(BMI)低于 25 kg/m2 的健康对照者进行了病例对照研究。我们使用基于 TaqMan 的检测方法对 10 个单核苷酸变异体 (SNV) 进行了基因分型。结果显示FOXO3A 中的四个 SNVs-rs1536057、AMPK 中的 rs103685、rs934778 和 POMC 中的 rs6545975 与 EOB 风险增加有关。其中,rs934778(POMC)的关联性最强,其最大比值比 (OR) 为 5.26(95% CI:2.86-9.09)。虽然这些基因变异与 EOB 密切相关,但它们并不影响血清葡萄糖、甘油三酯、高密度脂蛋白、低密度脂蛋白、体重指数或腰围。结论:这些研究结果表明,传统代谢途径之外的因素(可能与进食行为或激素调节有关)也可能将这些基因变异与肥胖联系在一起。要验证这些发现并探索其指导临床干预和公共卫生策略的潜力,必须在更大样本中开展进一步研究。
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来源期刊
Journal of Obesity
Journal of Obesity ENDOCRINOLOGY & METABOLISM-
CiteScore
7.50
自引率
3.00%
发文量
19
审稿时长
21 weeks
期刊介绍: Journal of Obesity is a peer-reviewed, Open Access journal that provides a multidisciplinary forum for basic and clinical research as well as applied studies in the areas of adipocyte biology & physiology, lipid metabolism, metabolic syndrome, diabetes, paediatric obesity, genetics, behavioural epidemiology, nutrition & eating disorders, exercise & human physiology, weight control and health risks associated with obesity.
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