Insulin gene variable number of tandem repeats (INS VNTR) genotype and metabolic syndrome in childhood obesity.
OBJECTIVE
The insulin variable number of tandem repeats (VNTR) polymorphism located in the insulin gene promoter (INS VNTR) has been associated with insulin levels in obese children. Hyperinsulinemia is a pivotal factor in the development of metabolic syndrome, an emerging complication in childhood obesity. With the present study, we aimed to test the associations between INS VNTR and the metabolic syndrome in juvenile-onset obesity.


METHODS
We screened for the INS VNTR in 320 obese children (152 girls; mean age, 11.2 +/- 2.3 yr; mean z-score body mass index, 3.6 +/- 1.1). All of them underwent a standard oral glucose tolerance test; baseline measurements included blood pressure and plasma lipid and fasting insulin levels. By using the data derived from the oral glucose tolerance test, the whole-body insulin sensitivity and the insulinogenic index were calculated.


RESULTS
The prevalence of metabolic syndrome reached 39%. No differences in INS VNTR genotype distribution were observed between obese subjects and 200 lean, age- and sex-matched children (P = 0.7). Among obese subjects, the prevalence of the metabolic syndrome was significantly higher in subjects with the I/I genotype (P = 0.006); the risk for developing the metabolic syndrome was significantly higher in subjects carrying the I/I genotype (odds ratio, 2.5; 95% confidence interval, 1.5-3.9). Obese subjects homozygous for the class I allele showed higher insulin levels and insulinogenic index but lower whole-body insulin sensitivity.


CONCLUSIONS
We conclude that the I variant of the insulin promoter, when expressed in homozygotes, can predispose obese children to develop the metabolic syndrome.
Santoro
Nicola
N
Department of Pediatrics, F. Fede Seconda Università di Napoli, Via Luigi De Crecchio No. 2, 80138 Napoli, Italy.
Cirillo
Grazia
G
Amato
Alessandra
A
Luongo
Caterina
C
Raimondo
Paolo
P
D'Aniello
Antonietta
A
Perrone
Laura
L
Miraglia del Giudice
Emanuele
E
D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000078790:Insulin Secretion; D024821:Metabolic Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D015995:Prevalence; D020080:Tandem Repeat Sequences
D001786:Blood Glucose; D005819:Genetic Markers; D007328:Insulin