Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults
Andrew P Demidowich, Viraj J Parikh, Nicket Dedhia, Rachel E Branham, Samar A Madi, Shannon E Marwitz, Robin B Roberson, Andrew J Uhlman, Noah J Levi, Sarah J Mi, Joo Yun Jun, Miranda M Broadney, Sheila M Brady, Jack A Yanovski, Andrew P Demidowich, Viraj J Parikh, Nicket Dedhia, Rachel E Branham, Samar A Madi, Shannon E Marwitz, Robin B Roberson, Andrew J Uhlman, Noah J Levi, Sarah J Mi, Joo Yun Jun, Miranda M Broadney, Sheila M Brady, Jack A Yanovski
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Trial registration: ClinicalTrials.gov NCT02153983 NCT01851421 NCT00030238 NCT00001522.
Keywords: body mass index; fat mass; genetic variation; genotype; homozygote; inflammation; lean mass; melanocortin 3 receptor; missense variants; obesity.
© 2019 John Wiley & Sons Ltd/University College London.
Source: PubMed