This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heude, B. Articles by Ong, K. K. Search for Related Content PubMed PubMed Citation Articles by Heude, B. Articles by Ong, K. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM UniGene Compound via MeSH Substance via MeSH Related Collections Pediatric Endocrinology Metabolism Obesity

The Insulin Gene Variable Number of Tandem Repeat: Associations and Interactions with Childhood Body Fat Mass and Insulin Secretion in Normal Children

Medical Research Council Epidemiology Unit (B.H., K.K.O.), Cambridge CB1 8RN, United Kingdom; Department of Pediatrics (C.J.P., D.B.D., K.K.O.), University of Cambridge, Cambridge CB2 2QQ, United Kingdom; Unit of Pediatric and Perinatal Epidemiology (ALSPAC study team), Department of Community Based Medicine, University of Bristol, Bristol BS8 1TQ, United Kingdom; and Clinical and Molecular Genetics Unit (M.P.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom

Address all correspondence and requests for reprints to: Dr. Ken Ong, Medical Research Council Epidemiology Unit, Strangeways Research Laboratory, Wort’s Causeway, Cambridge CB1 8RN, United Kingdom. E-mail: ken.ong{at}mrc-epid.cam.ac.uk.

Context: Polymorphism at the insulin gene (INS) variable number of tandem repeat (VNTR) shows variable associations with childhood body mass index (BMI) in different populations.

Objective: The objective of this study was to observe INS VNTR associations with body composition and insulin secretion in children.

Design: The study was designed as a prospective birth cohort study.

Participants: A total of 947 children genotyped for the INS VNTR participated.

Main Outcome Measures: Main outcome measures were whole body dual x-ray emission absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr.

Results: Homozygous III/III children had higher BMI (P = 0.020), FMI (P = 0.015), and truncal FMI (P = 0.022) at 9 yr than class I bearers, but no difference in fat-free mass (P = 0.23). Gain in weight SD score between birth and 3 yr was associated positively with BMI, FMI, and truncal FMI in class I bearers, but not in III/III children (p-interaction with genotype = 0.009–0.066). INS VNTR genotype was not associated overall with insulin secretion at 8 yr (P = 0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8 yr (regression coefficient ± SE, 0.26 ± 0.05; P < 0.0001) than III/III children (–0.10 ± 0.07; P = 0.48) (p-interaction = 0.003).

Conclusion: We clarified that the overall association between INS VNTR class III/III genotype and larger BMI in this population relates to fat mass, but not fat-free mass. In contrast, among the subgroup of children who showed rapid infancy weight gain, class I bearers tended to have larger BMI and fat mass than III/III children. This genetic interaction could relate to insulin secretion, which, in class I bearers, increased more rapidly with overweight and obesity.

This article has been cited by other articles:

				P. Bougneres Genotypic and phenotypic complexity at the insulin variable number of tandem repeats locus. J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4246 - 4249. [Full Text] [PDF]