Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Virchowstr. 174, 45147, Essen, Germany.
Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Sci Rep. 2023 Jun 27;13(1):10419. doi: 10.1038/s41598-023-37344-1.
Recent studies reported an impact of the melanocortin 3 receptor (MC3R) on the regulation of body weight, linear growth and puberty timing. Previously, allele p.44Ile of a frequent non-synonymous variant (NSV) p.Val44Ile was reported to be associated with decreased lean body mass (LBM) and later puberty in both sexes. We Sanger sequenced the coding region of MC3R in 185 children or adolescents with short normal stature (SNS) or 258 individuals with severe obesity, and 192 healthy-lean individuals. Eleven variants (six NSVs) were identified. In-silico analyses ensued. Three rare loss-of-function (LoF) variants (p.Phe45Ser, p.Arg220Ser and p.Ile298Ser) were only found in severely obese individuals. One novel highly conserved NSV (p.Ala214Val), predicted to increase protein stability, was detected in a single lean female. In the individuals with SNS, we observed deviation from Hardy-Weinberg Equilibrium (HWE) (p = 0.012) for p.Val44Ile (MAF = 11.62%). Homozygous p.44Ile carriers with SNS had an increased BMI, but this effect did not remain significant after Bonferroni correction. In line with previous findings, the detected LoF NSVs may suggest that dysfunction in MC3R is associated with decreased body height, obesity and delayed puberty.
最近的研究报告称，黑皮质素 3 受体（MC3R）对体重、线性生长和青春期时间的调节有影响。先前有研究报道，一种常见的非同义变异（NSV）p.Val44Ile 的等位基因 p.44Ile 与两性的瘦体重（LBM）减少和青春期延迟有关。我们对 185 名身材矮小正常的儿童或青少年（SNS）或 258 名严重肥胖者以及 192 名健康瘦个体的 MC3R 编码区进行了 Sanger 测序。共发现 11 个变异（6 个 NSV），并进行了计算机分析。三种罕见的失活（LoF）变异（p.Phe45Ser、p.Arg220Ser 和 p.Ile298Ser）仅在严重肥胖者中发现。在一个单独的瘦女性中发现了一种新的高度保守的 NSV（p.Ala214Val），预测其能增加蛋白质稳定性。在 SNS 个体中，我们观察到 p.Val44Ile 偏离 Hardy-Weinberg 平衡（HWE）（p=0.012）（MAF=11.62%）。SNS 患者中 p.44Ile 纯合子携带者 BMI 增加，但在 Bonferroni 校正后，这种影响不再显著。与先前的发现一致，检测到的 LoF NSV 可能表明 MC3R 功能障碍与身高降低、肥胖和青春期延迟有关。
