title: MC4R variant is associated with BMI but not response to resistance training in young females.
abstract: Recently, a genome-wide association study (GWAS) that identified eight single-nucleotide polymorphisms (SNPs) associated with BMI highlighted a possible neuronal influence on the development of obesity. We hypothesized these SNPs would govern the response of BMI and subcutaneous fat to resistance training in young individuals (age = 24 years). We genotyped the eight GWAS-identified SNPs in the article by Willer et al. in a cohort (n = 796) that undertook a 12-week resistance-training program. Females with a copy of the rare allele (C) for rs17782313 (MC4R) had significantly higher BMIs (
  n = 174; 24.70 ± 0.33 kg/m², TT: n = 278; 23.41 ± 0.26 kg/m², P = 0.002), and the SNP explained 1.9% of overall variation in BMI. Males with a copy of the rare allele (T) for rs6548238 (TMEM18) had lower amounts of subcutaneous fat pretraining (CT/TT: n = 65; 156,534 ± 7,415 mm³, CC: n = 136; 177,825 ± 5,139 mm³, P = 0.019) and males with a copy of the rare allele (A) for rs9939609 (FTO) lost a significant amount of subcutaneous fat with exercise (
  n = 83; -798.35 ± 2,624.30 mm³, TT: n = 47; 9,435.23 ± 3,494.44 mm³, P = 0.021). Females with a copy of the G allele for a missense variant in the SH2B1 (rs7498665) was associated with less change of subcutaneous fat volume with exercise (
  n = 191; 9,813 ± 2,250 mm³ vs. AA: n = 126; 770 ± 2,772 mm³; P = 0.011). These data support the original finding that there is an association between measures of obesity and a variant near the MC4R gene and extends these results to a younger population and implicates FTO, TMEM18, and SH2B1 polymorphisms in subcutaneous fat regulation.
authors: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA. fsuer@cnmcresearch.org
authors: Funda E
authors: FE
authors: Orkunoglu-Suer
authors: Brennan T
authors: BT
authors: Harmon
authors: Heather
authors: H
authors: Gordish-Dressman
authors: Priscilla M
authors: PM
authors: Clarkson
authors: Paul D
authors: PD
authors: Thompson
authors: Theodore J
authors: TJ
authors: Angelopoulos
authors: Paul M
authors: PM
authors: Gordon
authors: Monica J
authors: MJ
authors: Hubal
authors: Niall M
authors: NM
authors: Moyna
authors: Linda S
authors: LS
authors: Pescatello
authors: Paul S
authors: PS
authors: Visich
authors: Robert F
authors: RF
authors: Zoeller
authors: Eric P
authors: EP
authors: Hoffman
authors: Joseph M
authors: JM
authors: Devaney
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D015444:Exercise / Q000502:physiology*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D055070:Resistance Training; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000378:metabolism*; D055815:Young Adult
chemical_list: D044105:Receptor, Melanocortin, Type 4