Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes

Adrian Vella, N. Bouatia-Naji, B. Heude, J. D. Cooper, C. E. Lowe, C. Petry, S. M. Ring, D. B. Dunger, J. A. Todd, K. K. Ong

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Abstract

Aims/hypothesis: 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. Materials and 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) ≥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≥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/interpretation: Common genetic variation in IGF1 alters IGF-1 concentrations but is not associated with growth, glucose metabolism or type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)811-815
Number of pages5
JournalDiabetologia
Volume51
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Type 1 Diabetes Mellitus
Insulin-Like Growth Factor I
Single Nucleotide Polymorphism
Growth
Genes
Islets of Langerhans
Gene Frequency
Exons
Insulin
Phenotype
Glucose
Somatomedins
Introns
Longitudinal Studies
Cell Survival
Intercellular Signaling Peptides and Proteins
Parents

Keywords

  • Children
  • Genetic variation
  • Growth
  • IGF-1
  • Insulin-like growth factor-1
  • Microsatellite
  • Single nucleotide polymorphism
  • SNP
  • Tag-SNPs
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Vella, A., Bouatia-Naji, N., Heude, B., Cooper, J. D., Lowe, C. E., Petry, C., ... Ong, K. K. (2008). Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes. Diabetologia, 51(5), 811-815. https://doi.org/10.1007/s00125-008-0970-7

Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes. / Vella, Adrian; Bouatia-Naji, N.; Heude, B.; Cooper, J. D.; Lowe, C. E.; Petry, C.; Ring, S. M.; Dunger, D. B.; Todd, J. A.; Ong, K. K.

In: Diabetologia, Vol. 51, No. 5, 05.2008, p. 811-815.

Research output: Contribution to journalArticle

Vella, A, Bouatia-Naji, N, Heude, B, Cooper, JD, Lowe, CE, Petry, C, Ring, SM, Dunger, DB, Todd, JA & Ong, KK 2008, 'Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes', Diabetologia, vol. 51, no. 5, pp. 811-815. https://doi.org/10.1007/s00125-008-0970-7
Vella, Adrian ; Bouatia-Naji, N. ; Heude, B. ; Cooper, J. D. ; Lowe, C. E. ; Petry, C. ; Ring, S. M. ; Dunger, D. B. ; Todd, J. A. ; Ong, K. K. / Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes. In: Diabetologia. 2008 ; Vol. 51, No. 5. pp. 811-815.
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abstract = "Aims/hypothesis: 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. Materials and 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) ≥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≥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/interpretation: Common genetic variation in IGF1 alters IGF-1 concentrations but is not associated with growth, glucose metabolism or type 1 diabetes.",
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AU - Heude, B.

AU - Cooper, J. D.

AU - Lowe, C. E.

AU - Petry, C.

AU - Ring, S. M.

AU - Dunger, D. B.

AU - Todd, J. A.

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