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Insulin gene variable number of tandem repeats is not associated with weight from fetal life until infancy: the Generation R Study

¹ The Generation R Study Group, ² Department of Epidemiology and Biostatistics, ³ Department of Obstetrics and Gynaecology and ⁴ Department of Pediatrics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands

(Correspondence should be addressed to V W V Jaddoe; Email: v.jaddoe{at}erasmusmc.nl)

Objective: The aim of this study was to examine whether the insulin gene variable number of tandem repeats (INS VNTR) is associated with growth patterns in fetal life and infancy.

Design and methods: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood. Fetal growth was assessed by ultrasounds in early, mid-, and late pregnancy. Anthropometry in infancy was assessed at birth and at the ages of 6 weeks, 6 months, and 14 months. DNA for genotyping of the INS VNTR promoter region was available in 859 children.

Results: The genotype distribution was I/I 50.8%, I/III 40.0%, and III/III 9.2%. III/III individuals had a shorter gestational age (P<0.005 versus I/I) and a lower birth weight (P<0.05 versus I/I). There were no differences in birth weight after adjusting for gestational age. Class III homozygotes had a smaller abdominal circumference/head circumference (HC) ratio (P<0.005 versus I/I) in mid-pregnancy, but not in late pregnancy. Also, III/III subjects had a relative decrease in HC (SDS) from mid-pregnancy to the age of 14 months (P<0.05 versus I/I). No other differences in pre- and postnatal growth characteristics and patterns were found.

Conclusions: Class III homozygotes were born at an earlier gestational age. No association was found between INS VNTR and birth weight adjusted for gestational age. Our data suggest that the III/III genotype may be associated with asymmetrical growth in mid-pregnancy, but not in late pregnancy.