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Lack of Support for a Role of the Insulin Gene Variable Number of Tandem Repeats Minisatellite ( INS -VNTR) Locus in Fetal Growth or Type 2 Diabetes-Related Intermediate Traits in United Kingdom Populations

2004; Oxford University Press; Volume: 89; Issue: 1 Linguagem: Inglês

10.1210/jc.2003-030605

1945-7197

Simon M.S. Mitchell, Andrew T. Hattersley, Beatrice Knight, Tina Turner, Bradley S. Metcalf, L D Voss, David Davies, Anne McCarthy, Terence J. Wilkin, George Davey Smith, Yoav Ben‐Shlomo, Timothy M. Frayling,

Pancreatic function and diabetes

The insulin gene variable number of tandem repeats minisatellite (INS-VNTR) class III allele is associated with altered fetal growth, type 2 diabetes risk (especially when paternally inherited), and insulin and IGF2 gene expression. Further studies are needed to establish the role of the INS-VNTR in fetal growth and assess whether its effects depend on the parent of origin. We analyzed the INS-VNTR-linked −23 Hph1 polymorphism in 2283 subjects, comprising 1184 children and 1099 parents. There were no differences (P < 0.05) in birth weight between offspring of the three genotypes: III/III (n = 108) vs. I/I (n = 558), effect size, −8 g (P = 0.87); and I/III (n = 464) vs. I/I, effect size, −19 g (P = 0.54). We observed no differences in head circumference [III/III (n = 95) vs. I/I (n = 470), effect size, −0.14 cm; P = 0.31] or birth length. No differences were observed when stratifying by postnatal growth realignments [nonchangers III/III (n = 37) vs. I/I (n = 170), effect size, −43 g; P = 1.00] or by parent of origin of the class III allele (presence of paternal III allele effect size, −15 g; P = 0.74). INS-VNTR was nominally associated (P < 0.05) with body mass index and insulin resistance, but not with β-cell function, in young adults. In the largest study to date, we found a lack of support for a role for INS-VNTR in fetal growth and nominal association with type 2 diabetes-related intermediate traits.