Résumé :
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[BDSP. Notice produite par INIST-CNRS nR0xoqD9. Diffusion soumise à autorisation]. Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHRd3) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHRfl-d3 and GHRd3-d3 genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data. The primary outcome was the 1-year change-in-height standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies (1,527 children) were included. After several prior assumptions were tested, the most appropriate inheritance model was codominant (posterior probability =0.93). Compared with noncarriers, carriers had median differences in 1-year change-in-height standard-deviation score of 0.09 (95 % credible interval (Crl) : 0.01,0.17) for GHRfl-d3 and of 0.14 (95 % Crl : 0.02,0.26) for GHRd3-d3. However, the between-study standard deviation of 0.18 (95 % Crl : 0.10,0.33) was considerable. The authors tested by meta-regression for potential modifiers and found no substantial influence. They conclude that 1) the GHRd3 polymorphism inheritance is codominant, contrasting with previous reports ; 2) GHRd3 genotypes account for modest increases in rhGH effects in children ; and 3) considerable unexplained variability in responsiveness remains.
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