Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA

Laura Audí; Cristina Esteban; Antonio Carrascosa; Rosa Espadero; Annalisa Pérez-Arroyo; Rosa Arjona; María Clemente; Hartmut Wollmann; Linda Fryklund; Luis A. Parodi; J. Ajram; A. Aragones; A. Arroyos; A. Balaguer; M. J. Ballester; J. Bel; M. V. Borrás; J. Bosch; N. Cabrinety; M. Caimarí; M. Camprubí; P. Cantero; R. Cañete; G. Cao; G. Carreras; R. Corripio; A. De Ureta; C. J. De Valle; R. Espigares; A. Feliu; C. Fernández; J. Ferragut; A. Ferrández; A. Ferrer; M. E. Gallego; A. Gómez; J. P. González; R. Gracia; G. Grau; M. Gussinyé; P. Gutierrez; M. T. Herráez; L. Ibáñez; J. I. Labarta; J. L. Lechuga; G. Lledó; A. Llusà; R. López; J. P. López-Siguero; L. Lorenzo; C. Luzuriaga; A. Mainou; M. V. Marcos; M. J. Martínez-Aedo; P. Martul; E. Mayayo; A. Montesdeoca; R. Nosas; A. Oliver; M. J. Pisonero; N. Pons; J. M. Rial; I. Rica; S. Rite; J. Rodrigo; F. Rodríguez Hierro; A. Rodríguez; I. Rodríguez; A. Romo; J. Sánchez Del Pozo; E. Sastre; B. Sinués; B. Sobradillo; J. Tacons; A. Vela; E. Vicens-Calvet

doi:10.1210/jc.2006-0828

Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA

Laura Audí, Cristina Esteban, Antonio Carrascosa, Rosa Espadero, Annalisa Pérez-Arroyo, Rosa Arjona, María Clemente, Hartmut Wollmann, Linda Fryklund, Luis A. Parodi, J. Ajram, A. Aragones, A. Arroyos, A. Balaguer, M. J. Ballester, J. Bel, M. V. Borrás, J. Bosch, N. Cabrinety, M. CaimaríM. Camprubí, P. Cantero, R. Cañete, G. Cao, G. Carreras, R. Corripio, A. De Ureta, C. J. De Valle, R. Espigares, A. Feliu, C. Fernández, J. Ferragut, A. Ferrández, A. Ferrer, M. E. Gallego, A. Gómez, J. P. González, R. Gracia, G. Grau, M. Gussinyé, P. Gutierrez, M. T. Herráez, L. Ibáñez, J. I. Labarta, J. L. Lechuga, G. Lledó, A. Llusà, R. López, J. P. López-Siguero, L. Lorenzo, C. Luzuriaga, A. Mainou, M. V. Marcos, M. J. Martínez-Aedo, P. Martul, E. Mayayo, A. Montesdeoca, R. Nosas, A. Oliver, M. J. Pisonero, N. Pons, J. M. Rial, I. Rica, S. Rite, J. Rodrigo, F. Rodríguez Hierro, A. Rodríguez, I. Rodríguez, A. Romo, J. Sánchez Del Pozo, E. Sastre, B. Sinués, B. Sobradillo, J. Tacons, A. Vela, E. Vicens-Calvet

Research output: Contribution to journal › Article › Research › peer-review

57 Citations (Scopus)

Abstract

Context: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. Objective: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. Design: An adult control population with heights normally distributed (ACPNH) between -2 and +2 SD score (SDS) and a short non-GH-deficient SGA child population were selected. Setting: Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. Controls and Patients: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Main Outcome Measures: Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. Results: In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height ≤-1 SDS and ≥-2 SDS, n = 60). Conclusions: Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth. Copyright © 2006 by The Endocrine Society.

Original language	English
Pages (from-to)	5038-5043
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	91
Issue number	12
DOIs	https://doi.org/10.1210/jc.2006-0828
Publication status	Published - 1 Jan 2006

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Audí, L., Esteban, C., Carrascosa, A., Espadero, R., Pérez-Arroyo, A., Arjona, R., Clemente, M., Wollmann, H., Fryklund, L., Parodi, L. A., Ajram, J., Aragones, A., Arroyos, A., Balaguer, A., Ballester, M. J., Bel, J., Borrás, M. V., Bosch, J., Cabrinety, N., ... Vicens-Calvet, E. (2006). Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA. Journal of Clinical Endocrinology and Metabolism, 91(12), 5038-5043. https://doi.org/10.1210/jc.2006-0828

Audí, Laura ; Esteban, Cristina ; Carrascosa, Antonio ; Espadero, Rosa ; Pérez-Arroyo, Annalisa ; Arjona, Rosa ; Clemente, María ; Wollmann, Hartmut ; Fryklund, Linda ; Parodi, Luis A. ; Ajram, J. ; Aragones, A. ; Arroyos, A. ; Balaguer, A. ; Ballester, M. J. ; Bel, J. ; Borrás, M. V. ; Bosch, J. ; Cabrinety, N. ; Caimarí, M. ; Camprubí, M. ; Cantero, P. ; Cañete, R. ; Cao, G. ; Carreras, G. ; Corripio, R. ; De Ureta, A. ; De Valle, C. J. ; Espigares, R. ; Feliu, A. ; Fernández, C. ; Ferragut, J. ; Ferrández, A. ; Ferrer, A. ; Gallego, M. E. ; Gómez, A. ; González, J. P. ; Gracia, R. ; Grau, G. ; Gussinyé, M. ; Gutierrez, P. ; Herráez, M. T. ; Ibáñez, L. ; Labarta, J. I. ; Lechuga, J. L. ; Lledó, G. ; Llusà, A. ; López, R. ; López-Siguero, J. P. ; Lorenzo, L. ; Luzuriaga, C. ; Mainou, A. ; Marcos, M. V. ; Martínez-Aedo, M. J. ; Martul, P. ; Mayayo, E. ; Montesdeoca, A. ; Nosas, R. ; Oliver, A. ; Pisonero, M. J. ; Pons, N. ; Rial, J. M. ; Rica, I. ; Rite, S. ; Rodrigo, J. ; Rodríguez Hierro, F. ; Rodríguez, A. ; Rodríguez, I. ; Romo, A. ; Sánchez Del Pozo, J. ; Sastre, E. ; Sinués, B. ; Sobradillo, B. ; Tacons, J. ; Vela, A. ; Vicens-Calvet, E. / Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 12. pp. 5038-5043.

@article{6e4174f1cb1747e284532ac92ff3e580,

title = "Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA",

abstract = "Context: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. Objective: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. Design: An adult control population with heights normally distributed (ACPNH) between -2 and +2 SD score (SDS) and a short non-GH-deficient SGA child population were selected. Setting: Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. Controls and Patients: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Main Outcome Measures: Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. Results: In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height ≤-1 SDS and ≥-2 SDS, n = 60). Conclusions: Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth. Copyright {\textcopyright} 2006 by The Endocrine Society.",

author = "Laura Aud{\'i} and Cristina Esteban and Antonio Carrascosa and Rosa Espadero and Annalisa P{\'e}rez-Arroyo and Rosa Arjona and Mar{\'i}a Clemente and Hartmut Wollmann and Linda Fryklund and Parodi, {Luis A.} and J. Ajram and A. Aragones and A. Arroyos and A. Balaguer and Ballester, {M. J.} and J. Bel and Borr{\'a}s, {M. V.} and J. Bosch and N. Cabrinety and M. Caimar{\'i} and M. Camprub{\'i} and P. Cantero and R. Ca{\~n}ete and G. Cao and G. Carreras and R. Corripio and {De Ureta}, A. and {De Valle}, {C. J.} and R. Espigares and A. Feliu and C. Fern{\'a}ndez and J. Ferragut and A. Ferr{\'a}ndez and A. Ferrer and Gallego, {M. E.} and A. G{\'o}mez and Gonz{\'a}lez, {J. P.} and R. Gracia and G. Grau and M. Gussiny{\'e} and P. Gutierrez and Herr{\'a}ez, {M. T.} and L. Ib{\'a}{\~n}ez and Labarta, {J. I.} and Lechuga, {J. L.} and G. Lled{\'o} and A. Llus{\`a} and R. L{\'o}pez and L{\'o}pez-Siguero, {J. P.} and L. Lorenzo and C. Luzuriaga and A. Mainou and Marcos, {M. V.} and Mart{\'i}nez-Aedo, {M. J.} and P. Martul and E. Mayayo and A. Montesdeoca and R. Nosas and A. Oliver and Pisonero, {M. J.} and N. Pons and Rial, {J. M.} and I. Rica and S. Rite and J. Rodrigo and {Rodr{\'i}guez Hierro}, F. and A. Rodr{\'i}guez and I. Rodr{\'i}guez and A. Romo and {S{\'a}nchez Del Pozo}, J. and E. Sastre and B. Sinu{\'e}s and B. Sobradillo and J. Tacons and A. Vela and E. Vicens-Calvet",

year = "2006",

month = jan,

day = "1",

doi = "10.1210/jc.2006-0828",

language = "English",

volume = "91",

pages = "5038--5043",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "The Endocrine Society",

number = "12",

}

Audí, L, Esteban, C, Carrascosa, A, Espadero, R, Pérez-Arroyo, A, Arjona, R, Clemente, M, Wollmann, H, Fryklund, L, Parodi, LA, Ajram, J, Aragones, A, Arroyos, A, Balaguer, A, Ballester, MJ, Bel, J, Borrás, MV, Bosch, J, Cabrinety, N, Caimarí, M, Camprubí, M, Cantero, P, Cañete, R, Cao, G, Carreras, G, Corripio, R, De Ureta, A, De Valle, CJ, Espigares, R, Feliu, A, Fernández, C, Ferragut, J, Ferrández, A, Ferrer, A, Gallego, ME, Gómez, A, González, JP, Gracia, R, Grau, G, Gussinyé, M, Gutierrez, P, Herráez, MT, Ibáñez, L, Labarta, JI, Lechuga, JL, Lledó, G, Llusà, A, López, R, López-Siguero, JP, Lorenzo, L, Luzuriaga, C, Mainou, A, Marcos, MV, Martínez-Aedo, MJ, Martul, P, Mayayo, E, Montesdeoca, A, Nosas, R, Oliver, A, Pisonero, MJ, Pons, N, Rial, JM, Rica, I, Rite, S, Rodrigo, J, Rodríguez Hierro, F, Rodríguez, A, Rodríguez, I, Romo, A, Sánchez Del Pozo, J, Sastre, E, Sinués, B, Sobradillo, B, Tacons, J, Vela, A & Vicens-Calvet, E 2006, 'Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 12, pp. 5038-5043. https://doi.org/10.1210/jc.2006-0828

Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA. / Audí, Laura; Esteban, Cristina; Carrascosa, Antonio; Espadero, Rosa; Pérez-Arroyo, Annalisa; Arjona, Rosa; Clemente, María; Wollmann, Hartmut; Fryklund, Linda; Parodi, Luis A.; Ajram, J.; Aragones, A.; Arroyos, A.; Balaguer, A.; Ballester, M. J.; Bel, J.; Borrás, M. V.; Bosch, J.; Cabrinety, N.; Caimarí, M.; Camprubí, M.; Cantero, P.; Cañete, R.; Cao, G.; Carreras, G.; Corripio, R.; De Ureta, A.; De Valle, C. J.; Espigares, R.; Feliu, A.; Fernández, C.; Ferragut, J.; Ferrández, A.; Ferrer, A.; Gallego, M. E.; Gómez, A.; González, J. P.; Gracia, R.; Grau, G.; Gussinyé, M.; Gutierrez, P.; Herráez, M. T.; Ibáñez, L.; Labarta, J. I.; Lechuga, J. L.; Lledó, G.; Llusà, A.; López, R.; López-Siguero, J. P.; Lorenzo, L.; Luzuriaga, C.; Mainou, A.; Marcos, M. V.; Martínez-Aedo, M. J.; Martul, P.; Mayayo, E.; Montesdeoca, A.; Nosas, R.; Oliver, A.; Pisonero, M. J.; Pons, N.; Rial, J. M.; Rica, I.; Rite, S.; Rodrigo, J.; Rodríguez Hierro, F.; Rodríguez, A.; Rodríguez, I.; Romo, A.; Sánchez Del Pozo, J.; Sastre, E.; Sinués, B.; Sobradillo, B.; Tacons, J.; Vela, A.; Vicens-Calvet, E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 12, 01.01.2006, p. 5038-5043.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA

AU - Audí, Laura

AU - Esteban, Cristina

AU - Carrascosa, Antonio

AU - Espadero, Rosa

AU - Pérez-Arroyo, Annalisa

AU - Arjona, Rosa

AU - Clemente, María

AU - Wollmann, Hartmut

AU - Fryklund, Linda

AU - Parodi, Luis A.

AU - Ajram, J.

AU - Aragones, A.

AU - Arroyos, A.

AU - Balaguer, A.

AU - Ballester, M. J.

AU - Bel, J.

AU - Borrás, M. V.

AU - Bosch, J.

AU - Cabrinety, N.

AU - Caimarí, M.

AU - Camprubí, M.

AU - Cantero, P.

AU - Cañete, R.

AU - Cao, G.

AU - Carreras, G.

AU - Corripio, R.

AU - De Ureta, A.

AU - De Valle, C. J.

AU - Espigares, R.

AU - Feliu, A.

AU - Fernández, C.

AU - Ferragut, J.

AU - Ferrández, A.

AU - Ferrer, A.

AU - Gallego, M. E.

AU - Gómez, A.

AU - González, J. P.

AU - Gracia, R.

AU - Grau, G.

AU - Gussinyé, M.

AU - Gutierrez, P.

AU - Herráez, M. T.

AU - Ibáñez, L.

AU - Labarta, J. I.

AU - Lechuga, J. L.

AU - Lledó, G.

AU - Llusà, A.

AU - López, R.

AU - López-Siguero, J. P.

AU - Lorenzo, L.

AU - Luzuriaga, C.

AU - Mainou, A.

AU - Marcos, M. V.

AU - Martínez-Aedo, M. J.

AU - Martul, P.

AU - Mayayo, E.

AU - Montesdeoca, A.

AU - Nosas, R.

AU - Oliver, A.

AU - Pisonero, M. J.

AU - Pons, N.

AU - Rial, J. M.

AU - Rica, I.

AU - Rite, S.

AU - Rodrigo, J.

AU - Rodríguez Hierro, F.

AU - Rodríguez, A.

AU - Rodríguez, I.

AU - Romo, A.

AU - Sánchez Del Pozo, J.

AU - Sastre, E.

AU - Sinués, B.

AU - Sobradillo, B.

AU - Tacons, J.

AU - Vela, A.

AU - Vicens-Calvet, E.

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Context: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. Objective: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. Design: An adult control population with heights normally distributed (ACPNH) between -2 and +2 SD score (SDS) and a short non-GH-deficient SGA child population were selected. Setting: Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. Controls and Patients: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Main Outcome Measures: Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. Results: In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height ≤-1 SDS and ≥-2 SDS, n = 60). Conclusions: Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth. Copyright © 2006 by The Endocrine Society.

AB - Context: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. Objective: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. Design: An adult control population with heights normally distributed (ACPNH) between -2 and +2 SD score (SDS) and a short non-GH-deficient SGA child population were selected. Setting: Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. Controls and Patients: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Main Outcome Measures: Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. Results: In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height ≤-1 SDS and ≥-2 SDS, n = 60). Conclusions: Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth. Copyright © 2006 by The Endocrine Society.

U2 - 10.1210/jc.2006-0828

DO - 10.1210/jc.2006-0828

M3 - Article

VL - 91

SP - 5038

EP - 5043

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -

Audí L, Esteban C, Carrascosa A, Espadero R, Pérez-Arroyo A, Arjona R et al. Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA. Journal of Clinical Endocrinology and Metabolism. 2006 Jan 1;91(12):5038-5043. https://doi.org/10.1210/jc.2006-0828