Growth Hormone Receptor Polymorphism and Growth Hormone Therapy Response in Children: A Bayesian Meta-Analysis

被引:31
作者
Renehan, Andrew G. [1 ,2 ]
Solomon, Mattea [3 ]
Zwahlen, Marcel [4 ]
Morjaria, Reena [3 ]
Whatmore, Andrew [3 ]
Audi, Laura [5 ,6 ,7 ]
Binder, Gerhard [8 ]
Blum, Werner [9 ]
Bougneres, Pierre [10 ]
Dos Santos, Christine [10 ]
Carrascosa, Antonio [5 ,6 ,7 ]
Hokken-Koelega, Anita [11 ]
Jorge, Alexander [12 ]
Mullis, Primus E. [13 ]
Tauber, Maithe [14 ]
Patel, Leena [3 ]
Clayton, Peter E. [3 ]
机构
[1] Univ Manchester, Sch Canc & Enabling Sci, Manchester, Lancs, England
[2] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England
[3] Univ Manchester, Sch Biomed, Manchester, Lancs, England
[4] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland
[5] Hosp Valle De Hebron, Inst Recerca, Dept Pediat, Barcelona, Spain
[6] Autonomous Univ Barcelona, Barcelona, Spain
[7] Inst Salud Carlos III, Ctr Biomed Res Rare Dis CIBERER, Barcelona, Spain
[8] Univ Childrens Hosp, Tubingen, Germany
[9] Eli Lilly & Co, Lilly Res Labs, Bad Homburg, Germany
[10] Hop St Vincent de Paul, AP HP, Fac Med Paris Descartes, Dept Pediat Endocrinol, F-75674 Paris, France
[11] Erasmus MC Sophia Childrens Hosp, Dept Paediat, Div Endocrinol, Rotterdam, Netherlands
[12] Univ Sao Paulo, Fac Med, Div Endocrinol, Unit Endocrinol & Genet, Sao Paulo, Brazil
[13] Univ Childrens Hosp, Dept Paediat Endocrinol Diabetol & Metab, Bern, Switzerland
[14] Hop Enfants, Div Endocrinol Genet Gynaecol & Bone Dis, INSERM U543, Toulouse, France
关键词
Bayesian meta-analysis; genetic model; growth hormone; growth hormone receptor polymorphism; FOR-GESTATIONAL-AGE; IDIOPATHIC SHORT STATURE; EXON; 3; POLYMORPHISM; GH RECEPTOR; INCREASED RESPONSIVENESS; GENETIC MODEL; FINAL HEIGHT; BORN SMALL; DELETION; ISOFORMS;
D O I
10.1093/aje/kwr408
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
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 (GHR(d3)) 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 GHR(fl-d3) and GHR(d3-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 (CrI): 0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI: 0.02, 0.26) for GHR(d3-d3). However, the between-study standard deviation of 0.18 (95% CrI: 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 GHR(d3) polymorphism inheritance is codominant, contrasting with previous reports; 2) GHR(d3) genotypes account for modest increases in rhGH effects in children; and 3) considerable unexplained variability in responsiveness remains.
引用
收藏
页码:867 / 877
页数:11
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