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.
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 beta-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.
Mitchell
Simon M S
SM
Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom EX2 5AX.
Hattersley
Andrew T
AT
Knight
Beatrice
B
Turner
Tina
T
Metcalf
Bradley S
BS
Voss
Linda D
LD
Davies
David
D
McCarthy
Anne
A
Wilkin
Terence J
TJ
Smith
George Davey
GD
Ben-Shlomo
Yoav
Y
Frayling
Timothy M
TM
D000328:Adult; D000483:Alleles; D001724:Birth Weight / Q000235:genetics; D001827:Body Height; D015992:Body Mass Index; D002508:Cephalometry; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005220:Fathers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006128:Growth / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D006113:United Kingdom
D007328:Insulin; D007335:Insulin-Like Growth Factor II