Genetic study of the melanin-concentrating hormone receptor 2 in childhood and adulthood severe obesity.
BACKGROUND
The melanin-concentrating hormone receptor 2 (MCHR2) is a G protein-coupled receptor for melanin-concentrating hormone, a neuropeptide that plays an important role in feeding behaviors. MCHR2 maps on chromosome 6q16.3, in a susceptibility locus for childhood obesity.


OBJECTIVE
The aim of this study was to investigate the association between MCHR2 variation and human obesity.


METHODS
Case control and family-based studies were performed.


METHODS
A total of 141 obese children and 24 nonobese adult subjects was sequenced, and case-control analyses were conducted using 628 severely obese children and 1,401 controls.


RESULTS
There were 11 single nucleotide polymorphisms (SNPs) identified. We showed nominal association among -38,245 ATG A/G SNP (P = 0.03; 95% confidence interval 1.02-1.34; odds ratio 1.17), A76A T/C SNP (P = 0.03; 95% confidence interval 0.58-0.97; odds ratio 0.75), and childhood obesity. Analysis of 645 trios with childhood obesity supported further the A76A T/C association, showing an overtransmission to obese children of the at risk T allele (59.0%; P = 0.01), especially in children with most severe forms of obesity (Z score of body mass index > 4) (67.0%; P = 0.003). The A76A at risk T allele was also associated with overeating during meals (P = 0.02) in an additional group of 102 nonobese children. None of the MCHR2 variants, including the A76A SNP, showed association with adult severe obesity, although a trend for association of the T allele of this variant with food disinhibition (P = 0.06) and higher hunger (P = 0.09) was found. This variant was not associated with childhood obesity in an independent case-control study, including 1,573 subjects (P = 0.98). Moreover, the A76A SNP did not explain the linkage on the 6q locus.


CONCLUSIONS
Our results altogether suggest that MCHR2 is not a major contributor to polygenic obesity and support a modest effect of the A76A SNP on food intake abnormalities in childhood.
Ghoussaini
Maya
M
Centre National de la Recherche Scientifique Unité Mixte de Recherche 8090-Institute of Biology, Pasteur Institute, 59000 Lille, France.
Vatin
Vincent
V
Lecoeur
Cécile
C
Abkevich
Victor
V
Younus
Adib
A
Samson
Chantal
C
Wachter
Christophe
C
Heude
Barbara
B
Tauber
Maïté
M
Tounian
Patrick
P
Hercberg
Serge
S
Weill
Jacques
J
Levy-Marchal
Claire
C
Le Stunff
Catherine
C
Bougnères
Pierre
P
Froguel
Philippe
P
Meyre
David
D
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001066:Appetite / Q000502:physiology; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D004261:DNA Replication / Q000502:physiology; D005091:Exons / Q000235:genetics; D005247:Feeding Behavior; D001068:Feeding and Eating Disorders / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000523:psychology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011979:Receptors, Pituitary Hormone / Q000235:genetics*
C431280:MCHR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone