The promoter region of the adiponectin gene is a determinant in modulating insulin sensitivity in childhood obesity.
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.
Petrone
Antonio
A
Endocrinology, Department of Clinical Sciences, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy.
Zavarella
Sara
S
Caiazzo
Assunta
A
Leto
Gaetano
G
Spoletini
Marialuisa
M
Potenziani
Stella
S
Osborn
John
J
Vania
Andrea
A
Buzzetti
Raffaella
R
D052242:Adiponectin / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D005260:Female; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin