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The Promoter Region of the Adiponectin Gene Is a Determinant in Modulating Insulin Sensitivity in Childhood Obesity
Author(s) -
Petrone Antonio,
Zavarella Sara,
Caiazzo Assunta,
Leto Gaetano,
Spoletini Marialuisa,
Potenziani Stella,
Osborn John,
Vania Andrea,
Buzzetti Raffaella
Publication year - 2006
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2006.172
Subject(s) - adiponectin , insulin sensitivity , obesity , childhood obesity , medicine , endocrinology , insulin resistance , gene , insulin , promoter activity , promoter , biology , genetics , gene expression , overweight
Abstract We investigated the association of the − 11,391G>A, −11,377G>C, +45T>G , and + 276G>T adiponectin single‐nucleotide polymorphisms (SNPs) and expected haplotypes with the insulin resistance (IR) state in overweight/obese children; by using the haplotype background analysis, we also assessed the effect of each SNP independently. GG genotype at the −11,391 locus was associated with higher fasting insulin levels and homeostasis model assessment‐IR index and lower adiponectin levels compared with GA + AA genotypes ( p = 0.01, 0.002, and 0.03, respectively). Those heterozygous and homozygous for G allele at the −11,377 locus showed higher fasting glucose ( p = 0.001 for both), fasting insulin ( p = 0.001 for both), homeostasis model assessment‐IR index ( p < 0.001 for both), and triglyceride levels ( p = 0.02 and 0.03, respectively) and lower adiponectin levels ( p = 0.002 and 0.02, respectively) compared with C homozygotes. The +45G carriers showed higher fasting and 2‐hour glucose levels ( p = 0.01 for both) and lower adiponectin levels ( p = 0.02) compared with non‐carriers. Haplotype analysis suggested that, considering the same haplotypic background, each of the three polymorphisms exerted an independent effect on investigated parameters. The − 11,391G>A, −11,377C>G , and + 45T>G SNPs are associated with IR syndrome in overweight/obese children; they independently influence the investigated variables. The effect of + 45T>G SNP seems to be marginal compared with the promoter SNPs. The GGT haplotype is associated with the highest degree of IR.