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Association Analysis of Ten Candidate Genes in a Large Multinational Cohort of Small for Gestational Age Children and Children with Idiopathic Short Stature (NESTEGG study)

  • Background: Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. Patients and Methods: We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ and INS) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. Results: We found several clinical associations for GH1, GHR, IGF1, IGF1R, PPARγ and MAPK1. One SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. Conclusion:IGF1R SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS.

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Metadaten
Author: L.C.G. de Graaff, A.J.L. Clark, M. Tauber, M.B. Ranke, L.B. Johnston, J. Caliebe, C. Molinas, N. Amin, C. van Duijn, H. Wollmann, H. Wallaschofski, M.O. Savage, A.C.S. Hokken-Koelega
URN:urn:nbn:de:gbv:9-opus-32775
DOI:https://doi.org/10.1159/000355409
ISSN:1663-2818
ISSN:1663-2826
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24280783
Parent Title (English):Hormone Research in Paediatrics
Publisher:S. Karger AG
Place of publication:Basel, Switzerland
Document Type:Article
Language:English
Date of first Publication:2013/11/23
Release Date:2020/10/08
Tag:Birth length; Birth weight; Genotype; Gestational age; Growth hormone; Phenotype; Polymorphisms
GND Keyword:-
Volume:80
Issue:6
First Page:466
Last Page:476
Faculties:Universitätsmedizin / Institut für Klinische Chemie und Laboratoriumsmedizin
Licence (German):License LogoUrheberrechtlich geschützt