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The growth hormone receptor polymorphism in patients with acromegaly: relationship to BMI and glucose metabolism

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Abstract

The aim of this study was to investigate association between the frequencies of Growth Hormone receptor (d3GHR) gene polymorphisms and some clinical parameters of acromegalic patients. Total of 35 acromegalic patients were enrolled to study. The d3GHR polymorphism was identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose (FPG), Fasting insulin, HOMA-IR, IGF-I, GH, IGFBP3, triglyceride, HDL and LDL cholesterol concentrations were evaluated. The frequencies of d3GHR genotypes were found as follows; 5 (14.3%) subjects had d3/d3, 11 (31.4%) had d3/fl and 19 (54.3%) had fl/fl in patients. The prevalence of the d3 and fl alleles was 30 and 70%, respectively. Systolic blood pressure, fasting insulin and HOMA-IR was found significantly increased in homozygote d3GHR genotype group compared to d3/fl subjects (P < 0.05). In addition, BMI was observed significantly different among three genotypes (P = 0.007) and in the subjects with d3/d3 genotype, BMI was found significantly higher than d3/fl and fl/fl genotypes groups. As well as, no significant difference was found between the d3 and fl alleles group in terms of the clinical parameters except for BMI (P = 0.002). It can be said that the d3GHR gene polymorphism may affect BMI, systolic blood pressure and insulin regulation. At the same time we can say homozygote d3GHR genotype and d3 allele carriers may have more risk than other genotypes for high BMI.

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References

  1. Parkinson C, Ryder WD, Trainer PJ (2001) The relationship between serum GH and serum IGF-I in acromegaly is gender-specific. J Clin Endocrinol Metab 86:5240–5244

    Article  PubMed  CAS  Google Scholar 

  2. Ho KY, Evans WS, Blizzard RM, Veldhuis JD, Merriam GR, Samojlik E, Furlanetto R, Rogol AD, Kaiser DL, Thorner MO (1987) Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 64:51–58

    Article  PubMed  CAS  Google Scholar 

  3. Barkan AL, Halasz I, Dornfeld KJ, Jaffe CA, Friberg RD, Chandler WF, Sandler HM (1997) Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 82:3187–3191

    Article  PubMed  CAS  Google Scholar 

  4. Pantel J, Machinis K, Sobrier ML, Duquesnoy P, Goossens M, Amselem S (2000) Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution. J Biol Chem 275:18664–18669

    Article  PubMed  CAS  Google Scholar 

  5. Schmid C, Krayenbuehl PA, Bernays RL, Zwimpfer C, Maly FE, Wiesli P (2007) Growth hormone (GH) receptor isoform in acromegaly: lower concentrations of GH but not insulin-like growth factor-1 in patients with a genomic deletion of exon 3 in the GH receptor gene. Clin Chem 53:1484–1488

    Article  PubMed  CAS  Google Scholar 

  6. Dos Santos C, Essioux L, Teinturier C, Tauber M, Goffin V, Bougneres P (2004) A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone. Nat Genet 36:720–724

    Article  PubMed  CAS  Google Scholar 

  7. Binder G, Baur F, Schweizer R, Ranke MB (2006) The d3-growth hormone (GH) receptor polymorphism is associated with increased responsiveness to GH in Turner syndrome and short small-for-gestational-age children. J Clin Endocrinol Metab 91:659–664

    Article  PubMed  CAS  Google Scholar 

  8. Jorge AA, Marchisotti FG, Montenegro LR, Carvalho LR, Mendonca BB, Arnhold IJ (2006) Growth hormone (GH) pharmacokinetics: influence of GH receptor exon 3 retention or deletion on first-year growth response and final height in patients with severe GH deficiency. J Clin Endocrinol Metab 91:1076–1080

    Article  PubMed  CAS  Google Scholar 

  9. Mercado M, González B, Sandoval C, Esquenazi Y, Mier F, Vargas G, de los Monteros AL, Sosa E (2008) Clinical and biochemical impact of the d3 (fl) growth hormone receptor genotype in acromegaly. J Clin Endocrinol Metab 93(9):3411–3415

    Article  PubMed  CAS  Google Scholar 

  10. Bianchi A, Giustina A, Cimino V, Pola R, Angelini F, Pontecorvi A, De Marinis L (2009) Influence of growth hormone receptor d3 and full-lenght isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab 94(6):2015–2022

    Article  PubMed  CAS  Google Scholar 

  11. Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89:667–674

    Article  PubMed  CAS  Google Scholar 

  12. Montefusco L, Filopanti M, Ronchi CL, Olgiati L, La-Porta C, Losa M, Epaminonda P, Coletti F, Beck-Peccoz P, Spada A, Lania AG, Arosio M (2010) d3-Growth hormone receptor polymorphism in acromegaly: effects on metabolic phenotype. Clin Endocrinol 72:661–667

    Article  CAS  Google Scholar 

  13. Kamenicky P, Dos Santos C, Espinosa C, Salenave S, Galland F, Le Bouc Y, Maison P, Bougnères P, Chanson P (2009) D3 GH receptor polymorphism is not associated with IGF1 levels in untreated acromegaly. Eur J Endocrinol 161(2):231–235

    Article  PubMed  CAS  Google Scholar 

  14. Freda PU (2003) Current concepts in the biochemical assessment of the patient with acromegaly. Growth Horm IGF Res 13:171–184

    Article  PubMed  CAS  Google Scholar 

  15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  16. Lebovitz HE (2002) Insulin resistance and the insulin resistance syndrome. In: Clinician’s manual on insulin resistance. Science Press, London, pp 1–15

  17. Audi L, Esteban C, Carrascosa A, Espadero R, Perez-Arroyo A, Arjona R, Clemente M, Wollmann H, Fryklund L, Parodi LA (2006) Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-forgestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA. J Clin Endocrinol Metab 91:5038–5043

    Article  PubMed  CAS  Google Scholar 

  18. Qiu XS, Tang NL, Yeung HY, Qiu Y, Cheng JC (2007) Genetic association study of growth hormone receptor and idiopathic scoliosis. Clin Orthop Relat Res 462:53–58

    Article  PubMed  Google Scholar 

  19. Ko JM, Park JY, Yoo HW (2009) Common exon 3 polymorphism of the GH receptor (GHR) gene and effect of GH therapy on growth in Korean children with idiopathic short stature (ISS). Clin Endocrinol 70(1):82–87

    Article  CAS  Google Scholar 

  20. Strawbridge RJ, Karvestedt L, Li C, Efendic S, Ostenson CG, Gu HF, Brismar K (2007) GHR exon polymorphism: association type 2 diabetes mellitus and metabolic disorder. Growth Horm IGF Res 17:392–398

    Article  PubMed  CAS  Google Scholar 

  21. Kenth G, Shao Z, Cole DE, Goodyer CG (2007) Relationship of the human growth hormone receptor exon 3 genotype with final adult height and bone mineral density. J Clin Endocrinol Metab 92:725–728

    Article  PubMed  CAS  Google Scholar 

  22. Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25:102–152

    Article  PubMed  CAS  Google Scholar 

  23. Bondanelli M, Ambrosio MR, Uberti EC (2001) Pathogenesis and prevalence of hypertension in acromegaly. Pituitary 4:239–249

    Article  PubMed  CAS  Google Scholar 

  24. Moller J (2003) Effects of growth hormone on fluid homeostasis. Clinical and experimental aspects. Growth Horm IGF Res 13:55–74

    Article  PubMed  CAS  Google Scholar 

  25. Feld S, Hirschberg R (1996) Growth hormone, the insulin-like growth factor system, and the kidney. Endocr Rev 17:423–480

    PubMed  CAS  Google Scholar 

  26. Ranke MB, Partsch CJ, Lindberg A, Dorr HG, Bettendorf M, Hauffa BP, Schwarz HP, Mehls O, Sander S, Stahnke N, Steinkamp H, Said E, Sippell W (2002) Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001. Eur J Endocrinol 147:625–633

    Article  PubMed  CAS  Google Scholar 

  27. Binder G, Trebar B, Baur F, Schweizer R, Ranke MB (2008) Homozygosity of the d3-growth hormone receptor polymorphism is associated with a high total effect of GH on growth and a low BMI in girls with Turner syndrome. Clin Endocrinol 68:567–572

    Article  CAS  Google Scholar 

  28. Ko JM, Kim JM, Cheon CK, Kim DH, Lee DY, Cheong WY, Kim EY, Park MJ, Yoo HW (2010) The common exon 3 polymorphism of the growth hormone receptor gene and the effect of growth hormone therapy on growth in Korean patients with Turner syndrome. Clin Endocrinol 72(2):196–202

    Article  CAS  Google Scholar 

  29. Jensen RB, Vielwerth S, Larsen T, Greisen G, Leffers H, Juul A (2007) The presence of the d3-growth hormone receptor polymorphism is negatively associated with fetal growth but positively associated with postnatal growth in healthy subjects. J Clin Endocrinol Metab 92:2758–2763

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Medicine, Department of Physiology, University of Pamukkale, Denizli, 20070, Turkey

    Sebahat Turgut, Ceylan Ayada & Günfer Turgut

  2. Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology, University of Pamukkale, Denizli, Turkey

    Fulya Akın, Şenay Topsakal & Emrah Yerlikaya

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  1. Sebahat Turgut
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  2. Fulya Akın
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  3. Ceylan Ayada
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  4. Şenay Topsakal
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  5. Emrah Yerlikaya
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  6. Günfer Turgut
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Correspondence to Sebahat Turgut.

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Turgut, S., Akın, F., Ayada, C. et al. The growth hormone receptor polymorphism in patients with acromegaly: relationship to BMI and glucose metabolism. Pituitary 15, 374–379 (2012). https://doi.org/10.1007/s11102-011-0329-9

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