ELKH-DE Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Epidemiology and Surveillance Centre, Semmelweis University, 1085 Budapest, Hungary.
Int J Mol Sci. 2023 Mar 8;24(6):5209. doi: 10.3390/ijms24065209.
A specific phenotypic variant of obesity is metabolically healthy (MHO), which is characterized by normal blood pressure and lipid and glucose profiles, in contrast to the metabolically unhealthy variant (MUO). The genetic causes underlying the differences between these phenotypes are not yet clear. This study aims to explore the differences between MHO and MUO and the contribution of genetic factors (single nucleotide polymorphisms-SNPs) in 398 Hungarian adults (81 MHO and 317 MUO). For this investigation, an optimized genetic risk score (oGRS) was calculated using 67 SNPs (related to obesity and to lipid and glucose metabolism). Nineteen SNPs were identified whose combined effect was strongly associated with an increased risk of MUO (OR = 1.77, < 0.001). Four of them (rs10838687 in , rs693 in , rs1111875 in , and rs2000813 in ) significantly increased the risk of MUO (OR = 1.76, < 0.001). Genetic risk groups based on oGRS were significantly associated with the risk of developing MUO at a younger age. We have identified a cluster of SNPs that contribute to the development of the metabolically unhealthy phenotype among Hungarian adults suffering from obesity. Our findings emphasize the significance of considering the combined effect(s) of multiple genes and SNPs in ascertaining cardiometabolic risk in obesity in future genetic screening programs.
一种特定的肥胖表型变体是代谢健康（MHO），其特征是血压、血脂和血糖谱正常，与代谢不健康的变体（MUO）形成对比。这些表型之间差异的遗传原因尚不清楚。本研究旨在探讨 MHO 和 MUO 之间的差异，以及遗传因素（单核苷酸多态性-SNPs）在 398 名匈牙利成年人（81 名 MHO 和 317 名 MUO）中的贡献。为了进行这项研究，使用 67 个 SNPs（与肥胖以及血脂和血糖代谢相关）计算了优化的遗传风险评分（oGRS）。确定了 19 个 SNP，它们的综合效应与 MUO 的风险增加密切相关（OR=1.77， <0.001）。其中 4 个 SNP（位于 中的 rs10838687、rs693 中的 rs1111875、rs2000813 中的 rs2000813）显著增加了 MUO 的风险（OR=1.76， <0.001）。基于 oGRS 的遗传风险组与 MUO 发病年龄较小显著相关。我们已经确定了一组 SNP，它们有助于匈牙利肥胖成年人中代谢不健康表型的发展。我们的研究结果强调了在未来的遗传筛查计划中，考虑多个基因和 SNP 的综合效应对于确定肥胖中心血管代谢风险的重要性。
