Association study and mutation analysis of adiponectin shows association of variants in APM1 with complex obesity in women.
We performed an association study and mutation analysis of the adiponectin (APM1) gene to study its involvement in the development of obesity. We also studied the interaction with peroxisome proliferator-activated receptor gamma (PPARgamma). 223 obese women and 87 healthy female control subjects were used for association analysis. Mutation analysis was done on 95 morbidly obese adults and 123 overweight and obese children and adolescents. We selected 6 haplotype tagging SNPs in APM1 and the Pro12Ala variant (rs1805192) in PPARgamma to study the interaction. The G allele of rs2241766 was more common in controls (cases 10.8% vs. controls 18.4%, nominal p = 0.011; OR = 0.57, nominal p = 0.018). The rs2241766/rs3774261 haplotype was also associated with obesity (nominal p = 0.004). Only the latter association remained significant after controlling for the False Discovery Rate. Resequencing of exon 2, exon 3 and intron 2 in 95 individuals did not reveal any SNPs in high linkage disequilibrium with rs2241766. No interaction with the Pro12Ala variant in PPARgamma was detected. Mutation analysis of APM1 did not identify mutations. In conclusion, we found an association of an APM1 haplotype with obesity and found that APM1 mutations are not a common cause of monogenic obesity in our cohort.
Beckers
Sigri
S
Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, B-2610 Antwerp, Belgium.
Peeters
Armand V
AV
de Freitas
Fenna
F
Mertens
Ilse L
IL
Verhulst
Stijn L
SL
Haentjens
Dominique
D
Desager
Kristine N
KN
Van Gaal
Luc F
LF
Van Hul
Wim
W
D052242:Adiponectin / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001530:Belgium; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
C499918:ADIPOQ protein, human; D052242:Adiponectin; D047495:PPAR gamma