Demidowich Andrew P, Parikh Viraj J, Dedhia Nicket, Branham Rachel E, Madi Samar A, Marwitz Shannon E, Roberson Robin B, Uhlman Andrew J, Levi Noah J, Mi Sarah J, Jun Joo Yun, Broadney Miranda M, Brady Sheila M, Yanovski Jack A
Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD, 20892.
Office of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD, 20892.
Ann Hum Genet. 2019 Sep;83(5):355-360. doi: 10.1111/ahg.12315. Epub 2019 Apr 2.
The MC3R haplotype C17A + G241A, which encodes a partially inactivated receptor, has high prevalence in individuals of predominately African ancestry. In pediatric cohorts, homozygosity for this common variant has been associated with obesity, reduced lean mass, and greater fasting insulin. However, metabolic and body composition measures have not been well studied in adults with this haplotype.
A convenience sample of 237 healthy African-American adult volunteers was studied. TaqMan assays were used to genotype MC3R variants. Labs were drawn in the morning in the fasted state. Body composition data was obtained via dual-energy X-ray absorptiometry. An analysis of covariance was used to examine the associations of genotype with metabolic and body composition measures controlling for age and sex.
Individuals homozygous for the MC3R C17A + G241A haplotype had significantly greater body mass index, fat mass, fat mass percentage, and C-reactive protein, with reduced lean mass percentage as compared to heterozygous and wild-type participants (all ps < 0.05); fasting insulin was marginally nonsignificant between groups (p = 0.053). After adjusting for fat mass, laboratory differences no longer remained significant.
Homozygosity for MC3R C17A + G241A is associated with increased adiposity in African-American adults. Further studies are needed to elucidate the mechanisms behind these associations.
编码部分失活受体的MC3R单倍型C17A + G241A在主要为非洲血统的个体中具有较高的流行率。在儿科队列中，这种常见变异的纯合性与肥胖、瘦体重降低和空腹胰岛素水平升高有关。然而，在具有这种单倍型的成年人中，代谢和身体成分测量尚未得到充分研究。
对237名健康的非裔美国成年志愿者进行了便利抽样研究。使用TaqMan分析法对MC3R变异进行基因分型。在禁食状态下于早晨采集血样。通过双能X线吸收法获得身体成分数据。采用协方差分析来检验基因型与控制年龄和性别的代谢及身体成分测量之间的关联。
与杂合子和野生型参与者相比，MC3R C17A + G241A单倍型纯合子个体的体重指数、脂肪量、脂肪量百分比和C反应蛋白显著更高，而瘦体重百分比降低（所有p值<0.05）；两组之间的空腹胰岛素水平差异无统计学意义（p = 0.053）。在调整脂肪量后，实验室指标差异不再显著。
MC3R C17A + G241A纯合性与非裔美国成年人肥胖增加有关。需要进一步研究以阐明这些关联背后的机制。
