Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes.
OBJECTIVE
Insulin-like growth factor-1 is a major childhood growth factor and promotes pancreatic islet cell survival and growth in vitro. We hypothesised that genetic variation in IGF1 might be associated with childhood growth, glucose metabolism and type 1 diabetes risk. We therefore examined the association between common genetic variation in IGF1 and predisposition to type 1 diabetes, childhood growth and metabolism.


METHODS
Variants in IGF1 were identified by direct resequencing of the exons, exon-intron boundaries and 5' and 3' regions in 32 unrelated type 1 diabetes patients. A tagging subset of these variants was genotyped in a collection of type 1 diabetes families (3,121 parent-child trios). We also genotyped a previously reported CA repeat in the region 5' to IGF1. A subset of seven tag single nucleotide polymorphism (SNPs) that captured variants with minor allele frequency (MAF) > or =0.05 was genotyped in 902 children from the Avon Longitudinal Study of Parents And Children with data on growth, IGF-1 concentrations, insulin secretion and insulin action.


RESULTS
Resequencing detected 27 SNPs in IGF1, of which 11 had a MAF > 0.05 and were novel. Variants with MAF > or = 0.10 were captured by a set of four tag-SNPs. These SNPs showed no association with type 1 diabetes. In children, global variation in IGF1 was weakly associated with IGF-1 concentrations, but not with other phenotypes. The CA repeat in the region 5' to IGF1 showed no association with any phenotype.


CONCLUSIONS
Common genetic variation in IGF1 alters IGF-1 concentrations but is not associated with growth, glucose metabolism or type 1 diabetes.
Vella
A
A
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Bouatia-Naji
N
N
Heude
B
B
Cooper
J D
JD
Lowe
C E
CE
Petry
C
C
Ring
S M
SM
Dunger
D B
DB
Todd
J A
JA
Ong
K K
KK
D002648:Child; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006128:Growth / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010290:Parents; D020641:Polymorphism, Single Nucleotide
D017931:DNA Primers; D007334:Insulin-Like Growth Factor I; D004247:DNA