The Promoter Region of the Adiponectin Gene Is a Determinant in Modulating Insulin Sensitivity in Childhood Obesity

Abstract

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.

Adiponectin Level and Gene Variability Are Obesity and Metabolic Syndrome Markers in a Young Population

“…In contrast, some other studies demonstrated that the common -11377C allele was strongly associated with obesity and MetS parameters (17,52). Our findings are also consistent with previous reports in different populations and different age groups (53,54,55) stating that ADIPOQ gene may play an important role in MetS. Results of these reports pointed that regional differences in body fat affected the risk of metabolic abnormalities, and also ADIPOQ gene variants were suggested as modulators of visceral fat accumulation.…”

“…Identification of genes controlling adiponectin levels may aid our understanding of how genes influence MetS and possibly obesity (56). Many study results were published on associations of ADIPOQ SNPs (27,36,57) as well as haplotypes with plasma adiponectin concentrations (22,54), but the data are controversial. Association between serum adiponectin level and ADIPOQ variants represents one of the several mechanisms that can be considered as a link between ADIPOQ and MetS.…”

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study

“…According to previous studies 9, 18,19 we found standardized linkage disequilibrium between À11391 and À11377 SNPs. In this context, haplotype combinations could clarify associations involving these correlated markers.…”

“…Despite the low number of subjects measured for adiponectin levels, our results were in close agreement with other studies. [8][9][10]18,19 It has been previously described in different obese and nonobese populations that plasma concentrations of adiponectin are significantly higher in À11391A allele carriers, while À11377C4G ADIPOQ polymorphism induced lower adiponectin levels. Furthermore, transcriptional activity of the ADIPOQ promoter, measured with a luciferase assay, demonstrated that the À11391G4A polymorphism had a 2.5-fold increase in transcriptional activity, which was in accordance with higher adiponectin levels observed in À11391A carriers.…”

Effect of interaction betweenPPARG,PPARAandADIPOQgene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study

“…In an earlier study of SNP at the ADIPOQ locus -11391 G/A, -10066 G/A, -7734 A/C and + 276 G/T in this laboratory, we found -10066G, -11391A, -7734A and + 276T were significantly associated with higher serum adiponectin concentration in two large cohorts (104) . Association of elevated adiponectin with the -11391 A-allele has been reported widely (102,(105)(106)(107)(108) , although one group found lower adiponectin in G-allele carriers (109) . Associations between + 276G and lower adiponectin concentrations have also been reported in Spanish (110) , European (111) , Korean (112) and Japanese (113) subjects.…”