Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European- and African-American youth.
OBJECTIVE
Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity. This study aimed to assess the influence of the identified single nucleotide polymorphisms rs17782313 and rs17700633 on general and visceral adiposity in European- and African-American youth.


METHODS
In 1890 youth (49.1% European-American, 45.6% male, mean age 16.7 years), we examined the associations of the rs17782313 and rs17700633 with anthropometry, percent body fat, visceral adipose tissue, and subcutaneous abdominal adipose tissue. Interaction of the single nucleotide polymorphisms with ethnicity or sex was investigated and haplotype analyses conducted.


RESULTS
Rs17782313 was significantly associated with weight (P = .02) and waist circumference (P = .03) in all subjects and with body mass index (P = .002) in females. In females rs17700633 was significantly associated with percent body fat (P = .001), visceral adipose tissue (P < .001), and subcutaneous abdominal adipose tissue (P < .001). Rs17700633 was significantly associated with fasting insulin and homeostasis model assessment, but the significance attenuated after adjustment for percent body fat. These findings were confirmed by haplotype analysis. No significant interactions of the variants with ethnicity were found for any of these phenotypes.


CONCLUSIONS
The relatively large effect of these common variants near melanocortin 4 receptor on general and visceral adiposity in childhood, especially in girls, could prove helpful in elucidating the molecular mechanisms underlying the development of obesity in early life.
Liu
Gaifen
G
Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Zhu
Haidong
H
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
Lagou
Vasiliki
V
Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gutin
Bernard
B
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
Barbeau
Paule
P
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
Treiber
Frank A
FA
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
Dong
Yanbin
Y
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
Snieder
Harold
H
Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
D050154:Adiposity / Q000208:ethnology / Q000235:genetics*; D000293:Adolescent; D001741:Black or African American; D001835:Body Weight; D004247:DNA / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D050152:Intra-Abdominal Fat; D008297:Male; D009765:Obesity / Q000208:ethnology* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D014481:United States / Q000453:epidemiology
C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D004247:DNA