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SHR Neuro Cancer Cardio Lipid Metab Microb

Clayton, P; Bonnemaire, M; Dutailly, P; Maisonobe, P; Naudin, L; Pham, E; Zhang, Z; Grupe, A; Thiagalingam, A; Denèfle, P; EPIGROW Study Group.
Characterizing short stature by insulin-like growth factor axis status and genetic associations: results from the prospective, cross-sectional, epidemiogenetic EPIGROW study.
J Clin Endocrinol Metab. 2013; 98(6):E1122-E1130 Doi: 10.1210/jc.2012-4283 [OPEN ACCESS]
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Study Group Members Med Uni Graz:: Borkenstein Helmuth Martin
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Abstract:: Context: Serum IGF-I levels are often low in patients with short stature (SS) without defined etiology. Hence, genetic investigations have focused on the GH-IGF-I axis. Objective: Our objectives were to characterize IGF-I axis status and search for a broader range of genetic associations in children with SS and normal GH. Design and Setting: We conducted a prospective, cross-sectional, epidemiogenetic case-control study in 9 European countries (2008-2010). Participants: Children (n = 275) aged >= 2 years with SS without defined etiology (<=-2.5 height SD score [SDS]) and >= 1 peak GH >= 7 mu g/L) were recruited. Methods: Serum IGF-I, IGF-binding protein-3 (IGFBP-3), and acid-labile subunit (ALS) levels were measured in a central laboratory. Candidate gene exome sequencing was performed in this cohort and ethnicity-matched controls. Results: Serum IGF-I, IGFBP-3, and ALS levels were highly correlated, but there was a discrepancy between prevalence of IGF-I, IGFBP-3, and ALS deficiencies (53%, 30%, and 0.8%, respectively). An insertion-deletion (Indel) on the IGF1 gene (P = 1.2 x 10(-5), Bonferroni-corrected; case vs control frequency: 0.04 vs 0.112), an Indel on NFKB1 (P = 1.36 x 10(-10); case vs control frequency: 0.464 vs 0.272), and 2 single-nucleotide polymorphisms on ZBTB38 (P < 2.3 x 10(-6)) were associated with SS. At P < 10(-4), single-nucleotide polymorphisms on genes related to protein kinase regulation, MAPK, and Fanconi pathways were also associated with SS. Conclusions: IGF-I deficiency is a common feature in SS without defined etiology; an Indel in the IGF1 gene was associated with SS. However, genes involved in transcriptional regulation (NFKB1 and ZBTB38) and growth factor signaling were also associated, providing further candidates for genetic investigations on individual patients.
Find related publications in this database (using NLM MeSH Indexing): Body Height -; Child -; Child, Preschool -; Cross-Sectional Studies -; Female -; Growth Disorders - blood Growth Disorders - etiology Growth Disorders - genetics; Human Growth Hormone - blood; Humans -; Insulin-Like Growth Factor Binding Protein 3 - blood Insulin-Like Growth Factor Binding Protein 3 - deficiency; Insulin-Like Growth Factor I - analysis Insulin-Like Growth Factor I - deficiency Insulin-Like Growth Factor I - genetics; MAP Kinase Signaling System -; Male -; NF-kappa B p50 Subunit - genetics; Polymorphism, Single Nucleotide -; Prospective Studies -