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Association of the (CA)n repeat polymorphism of insulin‐like growth factor‐I and −202 A/C IGF‐binding protein‐3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

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Summary

Objective  A number of mathematical models for predicting growth and final height outcome have been proposed to enable the clinician to ‘individualize’ growth‐promoting treatment. However, despite optimizing these models, many patients with isolated growth hormone deficiency (IGHD) do not reach their target height. The aim of this study was to analyse the impact of polymorphic genotypes [CA repeat promoter polymorphism of insulin‐like growth factor‐I (IGF‐I) and the −202 A/C promoter polymorphism of IGF‐Binding Protein‐3 (IGFBP‐3)] on variable growth factors as well as final height in severe IGHD following GH treatment.

Design, Patients and Controls  One hundred seventy eight (IGF‐I) and 167 (IGFBP‐3) subjects with severe growth retardation because of IGHD were studied. In addition, the various genotypes were also studied in a healthy control group of 211 subjects.

Results  The frequency of the individual IGF‐I (CA)n repeats ranging from 10 to 24, with the most frequent allele containing CA19, was similar in controls and in IGHD subjects. However, in controls, the pooled CA19 and CA20 as well as −202 A IGFBP‐3 alleles were significantly (P < 0·01 and P < 0·001) more common in the taller [≥2 to 0 standard deviation score (SDS)] when compared with the shorter subgroup (<0 to ≤−2 SDS). Overall, the effect of recombinant human growth hormone (rhGH) replacement did not reveal any difference between the various genotypes in terms of final height. Independent of their genotype, all subjects showed a slightly lower adult height SDS compared with midparental height SDS.

Conclusion  Our results indicate that in patients with severe IGHD, although the various IGF‐I and IGFBP‐3 genotypes may play a role in GH responsiveness, there was no effect on final height.
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Document Type: Research Article

Affiliations: 1: Paediatric Endocrinology, University Children’s Hospital, Inselspital, Bern, Switzerland 2: Department of Medical Sciences, Università del Piemonte Orientale, Novara, Italy 3: Dipartimento di Scienze Pediatriche Università degli Studi di Pavia, Pavia, Italy 4: University College London Developmental Endocrinology Research Group, Institute of Child Health, London, UK

Publication date: May 1, 2012

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