Growth hormone pharmacogenetics: the interactive effect of a microsatellite in the IGF1 promoter region with the GHR-exon 3 and-202 A/C IGFBP3 variants on treatment outcomes of children with severe GH deficiency

Insulin-like growth factor type 1 (IGF1) is a mediator of growth hormone (GH) action, and therefore, IGF1 is a candidate gene for recombinant human GH (rhGH) pharmacogenetics. Lower serum IGF1 levels were found in adults homozygous for 19 cytosine-adenosine (CA) repeats in the IGF1 promoter. The aim of this study was to evaluate the influence of (CA)n IGF1 polymorphism, alone or in combination with GH receptor (GHR)-exon 3 and -202 A/C insulin-like growth factor binding protein-3 (IGFBP3) polymorphisms, on the growth response to rhGH therapy in GH-deficient (GHD) patients. Eighty-four severe GHD patients were genotyped for (CA) n IGF1, -202 A/C IGFBP3 and GHR-exon 3 polymorphisms. Multiple linear regressions were performed to estimate the effect of each genotype, after adjustment for other influential factors. We assessed the influence of genotypes on the first year growth velocity (1st y GV) (n = 84) and adult height standard deviation score (SDS) adjusted for target-height SDS (AH-TH SDS) after rhGH therapy (n = 37). Homozygosity for the IGF1 19CA repeat allele was negatively correlated with 1st y GV (P = 0.03) and AH-TH SDS (P = 0.002) in multiple linear regression analysis. In conjunction with clinical factors, IGF1 and IGFBP3 genotypes explain 29% of the 1st y GV variability, whereas IGF1 and GHR polymorphisms explain 59% of final height-target-height SDS variability. We conclude that homozygosity for IGF1 (CA) 19 allele is associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with severe GHD. Furthermore, this polymorphism exhibits a non-additive interaction with -202 A/C IGFBP3 genotype on the 1st y GV and with GHR-exon 3 genotype on adult height. The Pharmacogenomics Journal (2012) 12, 439-445; doi:10.1038/tpj.2011.13; published online 5 April 2011

The Interactive Effect of GHR-Exon 3 and -202 A/C IGFBP3 Polymorphisms on rhGH Responsiveness and Treatment Outcomes in Patients with Turner Syndrome

Context: There is great interindividual variability in the response to recombinant human (rh) GH therapy in patients with Turner syndrome (TS). Ascertaining genetic factors can improve the accuracy of growth response predictions. Objective: The objective of the study was to assess the individual and combined influence of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on the short-and long-term outcomes of rhGH therapy in patients with TS. Design and Patients: GHR-exon 3 and -202 A/C IGFBP3 genotyping (rs2854744) was correlated with height data of 112 patients with TS who remained prepubertal during the first year of rhGH therapy and 65 patients who reached adult height after 5 +/- 2.5 yr of rhGH treatment. Main Outcome Measures: First-year growth velocity and adult height were measured. Results: Patients carrying at least one GHR-d3 or -202 A-IGFBP3 allele presented higher mean first-year growth velocity and achieved taller adult heights than those homozygous for GHR-fl or -202 C-IGFBP3 alleles, respectively. The combined analysis of GHR-exon 3 and -202 A/C IGFBP3 genotypes showed a clear nonadditive epistatic influence on adult height of patients with TS treated with rhGH (GHR-exon 3 alone, R-2 = 0.27; -202 A/C IGFBP3, R-2 = 0.24; the combined genotypes, R-2 = 0.37 at multiple linear regression). Together with clinical factors, these genotypes accounted for 61% of the variability in adult height of patients with TS after rhGH therapy. Conclusion: Homozygosity for the GHR-exon3 full-length allele and/or the -202C-IGFBP3 allele are associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with TS. (J Clin Endocrinol Metab 97: E671-E677, 2012)

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

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.

Na 1 Nachlass Max Horkheimer, 16 - Korrespondenzen u.a. mit Gerhart Jacoby Gordon (p. I 8, 202-379)

2 Briefe von A. Gandon an Max Horkheimer, Februrar 1936; 1 Brief von Max Horkheimer an Lloyd K. Garrison, 25.03.1941; 4 Briefe zwischen Moritz Geiger und Max Horkheimer, 01.12.1935, 1935; 1 Lebenslauf von Alvin Johnsson an Friedrich Pollock; 1 Brief von Alvon Johnson an Friedrich Pollock, 39.09.1940; 1 Brief von Max Horkheimer an Harald Genssler, 04.09.1949; 1 Brief von der George Washington University Washington an Max Horkheimer, 01.03.1939; 2 Briefe von Wolfgang Gerloff an Max Horkheimer, 1934, 1939; 2 Briefe zwsichen Hans Gerth und Max Horkheimer, 28.10.1937, 16.11.1937; 1 Brief von M. Getzer anMax Horkheimer, 04.05.1934; 12 Briefe zwsichen Edgar V. M. Gilbert und Max Horkheimer, 1935-1940; 1 Brief von der Gillespie, Kinsports & Bears Travel Agency New York an Max Horkheimer, 16.04.1935; 1 Entwurf von Max Horkheimer an Morris Ginsberg, Dezember 1935; 19 Briefe zwsichen Morris Ginsberg, Ethel Ginsberg und Max Horkheimer, 1935-1938; 2 Briefe zwischen Robert Morrison MacIver und Max Horkheimer, 18.08.1937, 16.08.1937; 1 Brief von H. Girsberger an Max Horkheimer, 17.08.1938; 1 Brief von Max Horkheimer an Glass, 24.12.1940; 1 Brief von der Glidden Buick Corporation New York an Max Horkheimer, 05.06.1940; 1 Heiratsanzeige von Vera Gold; 4 Briefe zwischen Oskar Goldberg und Max Horkheimer, 1941, 27.08.1941; 10 Briefe zwischen Hans Goldmann und Max Horkheimer, 1934-1937; 14 Briefe zwischen Alfons Goldschmidt und Max Horkheimer, 1936-1938; 7 Briefe zwsichen dem Greater New York Coordinating Committee for German Refugees, New York und Max Horkheimer, 1937-1939; 1 Brief von Max Horkheimer an Simon Guggenheim, 24.01.1938; 3 Briefe zwischen Aron Goldschmidt und Max Horkheimer, 02.02.1939, Mai 1942; 2 Briefe zwischen Berta Goldschmidt und Max Horkheimer, 14.01.1941, 25.02.1941; 4 Briefe von Emma Goldschmidt an Juliette Favez, 1938-1940; 5 Briefe zwischen Emma Goldschmidt und Max Horkheimer, 1938-1940; 2 Briefe zwischen Ernst L. Goldschmidt und Max Horkheimer, 08.07.1937, 18.06.1937; 1 Brief von Thea Goldschmidt an Max Horkheimer, 16.04.1935; 14 Briefe zwischen Kurt Goldstein und Max Horkheimer, 1934-1941; 19 Briefe zwsichen Gerhart Jacoby Gordon und Max Horkheimer, 1934-1937;

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 202 - Kontaktaufnahme von Georg Friedrich Röding anlässlich der Nachricht über die Überreichung der goldenen Ehrenmedaillie von der "Königlichen Academie der Wissenschaften in Drontheim"

u.a.: Kontakt zu den Eltern Schopenhauers in Hamburg; Vers von Johanna Schopenhauer von 1802; Kaufmannsberuf;

Ms.Ff.F.Stoltze 3. 202 - Brief von ... Mylius an Friedrich Stoltze

Zu einem Stoltze-Gedicht

Ausst. 202 - Passio domini nostri Jesu, ex Hieronymo Paduano, Dominico Mancino, Sedulio et Baptista Mantuano per fratrem Chelidonium collecta, cum figuris Alberti Dureri Norici Pictoris

Vorbesitzer: Heinrich Anton Cornill-d'Orville (Exlibris im Vorderdeckel)

Ms. lat. oct. 202 - Berichte über die Sitzungen der Cortes

Vorbesitzer (?): F.B.S.