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

Abstract

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 midpregnancy, 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.European Journal of Endocrinology 157 741-748

Wpływ występowania allelu klasy III VNTR genu INS na parametry auksologiczne, stężenie glukozy, insuliny, lipidów i adipocytokin u przeddojrzewaniowych dzieci urodzonych z niską masą ciała

“…Among SGA children, similarly to results provided by others [14][15][16][17][18], we did not find any relationship as regards the examined variants of INS VNTR and birth weight or birth length. Although Lindsay et al [10] have reported that the class III allele is associated with a reduction of birth weight, we should be aware that the analysis was performed among Pima Indians, in whom high incidence of obesity, IR, and T2DM is observed, and the distribution of birth weight may be associated with these maternal factors.…”

“…It was proven that both in foetal and in adult pancreas, lower insulin mRNA expression in INS VNTR class III homozygous than in class I homozygous individuals is observed [6,7,9]. However, the potential effect of class III allele on birth weight is still controversial [10][11][12][13][14][15][16][17][18]. On the other hand, class III is protective against diabetes mellitus type 1 (T1DM) and leads to an overexpression of insulin [19][20][21].…”

The Generation R Study: design and cohort update 2012

“…Also, strategies for genetic scoring analyses are being developed to estimate predictive values of identified genetic variants [171,172]. Although a GWAS is available in children, we use DNA from both children and parents for genotyping for candidate gene or replication studies [173][174][175][176][177][178][179][180][181][182]. Missing data in DNA samples in children will be collected by blood sampling or other methods at follow-up measurements.…”

Insulin VNTR and IGF-1 Promoter Region Polymorphisms Are Not Associated with Body Composition in Early Childhood: The Generation R Study

“…Several studies have suggested that this polymorphism is associated with size at birth, childhood and adult obesity, type 2 diabetes and insulin resistance [3,4,5]. However, thus far, findings seem to be rather inconsistent [1,4,6]. We have previously found an association of INS VNTR with a gestational duration but not with birth weight [4].…”

“…INS VNTR is known to have functional effects on circulating insulin levels, which may influence fetal and early postnatal growth [2]. Several studies have suggested that this polymorphism is associated with size at birth, childhood and adult obesity, type 2 diabetes and insulin resistance [3,4,5]. However, thus far, findings seem to be rather inconsistent [1,4,6].…”