ROLE OF INSULIN VARIABLE NUMBER TANDEM REPEAT POLYMORPHISM IN CHILDHOOD OBESITY

Association studies between childhood obesity and insulin gene (INS) variable number tandem repeat (VNTR) polymorphisms have not been confirmed in large cohorts. The aim of the study was to search an association between INS VNTR and obesity related phenotypes (history of obesity and insulin resistance) in a large cohort of obese children. 392 obese children (13.4±4.2y, BMI Zscore 4.3±1.1SD) and 370 adult controls who never have been obese (48.9±6.7y, BMI 22.0±2.0 kg/m2) were genotyped for INS VNTR by PCR-RFLP. Phenotypic characterization was performed in all obese children (anthropometric measurements, weight history, fasting plasma insulin and glucose concentrations, fasting leptin). Frequencies of INS VNTR genotypes were similar in Caucasians obese children and controls (Caucasian children: I/I 51%, I/III 39%, III/III 10%; Controls: I/I 46%, I/III 43%, III/III 10%). In non Caucasian children, allelic frequencies were significantly different (I/I 15%, I/III 39%, III/III 46% p<0.0001). INS VNTR were not associated with obesity related phenotypes in Caucasian obese children (age of obesity onset: I/I 4.3±0.6y vs I/III and III/III 4.2±0.8y, NS; BMI Zscore: I/I 4.7±0.2 SD vs I/III and III/III 4.6±0.2 SD, NS; weight gain per year: I/I 5.9±0.2 kg vs I/III and III/III 6.1±0.2 kg, NS; fasting insulin concentrations: I/I 16.9±1.5 μU/ml vs I/III and III/III 14.6±1.4 μU/ml, NS; HOMA: I/I 3.7±0.3 vs I/III and III/III 3.2±0.3, NS; leptin adjusted to fat mass: I/I 28.1±2.1 ng/ml vs I/III and III/III 30.6±2.0 ng/ml) after adjustment for age, sex, and Tanner stage. INS VNTR are not associated to obesity history and insulin resistance in our cohort of severely obese children.