Background: Melanocortin 4 receptor (MC4R) is a G-protein-coupled receptor involved in appetite regulation. Mutations in the MC4R gene are the most common cause of monogenic obesity. More than 200 sequence variants in the MC4R gene have been associated with obesity, although the vast majority of these data have been obtained from populations of European ancestry. The prevalence and mutation profile of MC4R is thus poorly characterized in other ancestries/ethnicities. Materials and Methods: We surveyed the allele frequencies of the MC4R variants of multiple racial/ethnic populations represented in the Genome Aggregation Database (gnomAD) and sequenced the MC4R gene in a diverse population of 60 individuals with extreme obesity. Results: Allele frequencies were similar for most classes of variants except for a higher rate of synonymous substitutions in the African gnomAD population. We also identified two apparently novel MC4R variants and two variants with much higher allele frequencies in African populations whose functional impacts are not yet known. Conclusion: These results highlight the need for characterizing MC4R variants in diverse populations with extreme obesity.

中文翻译：

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不同种群中的黑皮质素4受体基因序列分析。

背景：黑皮质素4受体（MC4R）是参与食欲调节的G蛋白偶联受体。MC4R基因突变是导致单基因肥胖的最常见原因。尽管肥胖症的绝大多数数据来自欧洲血统，但MC4R基因中的200多个序列变异已与肥胖相关。因此，在其他祖先/族裔中，MC4R的患病率和突变特征很差。材料和方法：我们调查了基因组聚合数据库（gnomAD）中代表的多个种族/族裔群体的MC4R变体的等位基因频率，并对60个极端肥胖的不同人群中的MC4R基因进行了测序。结果：除了非洲gnomAD人群中同义替换的比率较高外，大多数类别变体的等位基因频率相似。我们还确定了两个明显新颖的MC4R变体和两个在非洲人群中等位基因频率更高的变体，其功能影响尚不清楚。结论：这些结果强调了在极端肥胖的不同人群中表征MC4R变异的必要性。