TY - JOUR
T1 - ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity
AU - Bouatia-Naji, Nabila
AU - Meyre, David
AU - Lobbens, Stéphane
AU - Séron, Karin
AU - Fumeron, Frédéric
AU - Balkau, Beverley
AU - Heude, Barbara
AU - Jouret, Béatrice
AU - Scherer, Philipp E.
AU - Dina, Christian
AU - Weill, Jacques
AU - Froguel, Philippe
PY - 2006/2
Y1 - 2006/2
N2 - Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding gene have been associated with insulin resistance and type 2 diabetes in several populations. Here, we investigate the role of SNPs -11,377C>G, -11,391G>A, +45T>G, and +276G>T in 2,579 French Caucasians (1,229 morbidly obese and 1,350 control subjects). We found an association between severe forms of obesity and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006). Surprisingly, alternative alleles -11,377G and +276G have been previously reported as risk factors for type 2 diabetes. Transmission disequilibrium tests showed a trend in overtransmission (56.7%) of a risk haplotype 1(C)-1(G)-1(T)-2(T) including -11,377C and +276T in 634 obesity trios (P = 0.097). Family-based analysis in 400 trios from the general population indicated association between obesity haplotype and higher adiponectin levels, suggesting a role of hyperadiponectinemia in weight gain. However, experiments studying the putative roles of SNPs -11,377C>G and +276G>T on ACDC functionality were not conclusive. In contrast, promoter SNP -11,391G>A was associated with higher adiponectin levels in obese children (P = 0.005) and in children from the general population (0.00007). In vitro transcriptional assays showed that -11,391A may increase ACDC activity. In summary, our study suggests that variations at the ACDC/adiponectin gene are associated with risk of severe forms of obesity. However, the mechanisms underlying these possible associations are not fully understood.
AB - Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding gene have been associated with insulin resistance and type 2 diabetes in several populations. Here, we investigate the role of SNPs -11,377C>G, -11,391G>A, +45T>G, and +276G>T in 2,579 French Caucasians (1,229 morbidly obese and 1,350 control subjects). We found an association between severe forms of obesity and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006). Surprisingly, alternative alleles -11,377G and +276G have been previously reported as risk factors for type 2 diabetes. Transmission disequilibrium tests showed a trend in overtransmission (56.7%) of a risk haplotype 1(C)-1(G)-1(T)-2(T) including -11,377C and +276T in 634 obesity trios (P = 0.097). Family-based analysis in 400 trios from the general population indicated association between obesity haplotype and higher adiponectin levels, suggesting a role of hyperadiponectinemia in weight gain. However, experiments studying the putative roles of SNPs -11,377C>G and +276G>T on ACDC functionality were not conclusive. In contrast, promoter SNP -11,391G>A was associated with higher adiponectin levels in obese children (P = 0.005) and in children from the general population (0.00007). In vitro transcriptional assays showed that -11,391A may increase ACDC activity. In summary, our study suggests that variations at the ACDC/adiponectin gene are associated with risk of severe forms of obesity. However, the mechanisms underlying these possible associations are not fully understood.
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U2 - 10.2337/diabetes.55.02.06.db05-0971
DO - 10.2337/diabetes.55.02.06.db05-0971
M3 - Article
C2 - 16443793
AN - SCOPUS:33644785980
SN - 0012-1797
VL - 55
SP - 545
EP - 550
JO - Diabetes
JF - Diabetes
IS - 2
ER -