We investigated the association of the Ϫ11,391GϾA, Ϫ11,377GϾC, ϩ45TϾG, and ϩ276GϾT 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 Ϫ11,391 locus was associated with higher fasting insulin levels and homeostasis model assessment-IR index and lower adiponectin levels compared with GA ϩ AA genotypes (p ϭ 0.01, 0.002, and 0.03, respectively). Those heterozygous and homozygous for G allele at the Ϫ11,377 locus showed higher fasting glucose (p ϭ 0.001 for both), fasting insulin (p ϭ 0.001 for both), homeostasis model assessment-IR index (p Ͻ 0.001 for both), and triglyceride levels (p ϭ 0.02 and 0.03, respectively) and lower adiponectin levels (p ϭ 0.002 and 0.02, respectively) compared with C homozygotes. The ϩ45G carriers showed higher fasting and 2-hour glucose levels (p ϭ 0.01 for both) and lower adiponectin levels (p ϭ 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 Ϫ11,391GϾA, Ϫ11,377CϾG, and ϩ45TϾG SNPs are associated with IR syndrome in overweight/obese children; they independently influence the investigated variables. The effect of ϩ45TϾG SNP seems to be marginal compared with the promoter SNPs. The GGT haplotype is associated with the highest degree of IR.
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