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

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 CA ₁₉, was similar in controls and in IGHD subjects. However, in controls, the pooled CA ₁₉ and CA ₂₀ 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 (