title: Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly.
abstract: BACKGROUND
  Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture.
  
  
  OBJECTIVE
  Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment.
  
  
  METHODS
  The study was conducted at a specialized clinic at a tertiary care hospital.
  
  
  METHODS
  We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR.
  
  
  METHODS
  We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics.
  
  
  RESULTS
  Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58).
  
  
  CONCLUSIONS
  The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.
authors.affiliation: Endocrine Section, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México City, México. mmercadoa@yahoo.com
authors.forename: Moisés
authors.initials: M
authors.lastname: Mercado
authors.forename: Baldomero
authors.initials: B
authors.lastname: González
authors.forename: Carolina
authors.initials: C
authors.lastname: Sandoval
authors.forename: Yoshua
authors.initials: Y
authors.lastname: Esquenazi
authors.forename: Fernando
authors.initials: F
authors.lastname: Mier
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Vargas
authors.forename: Ana Laura Espinosa
authors.initials: AL
authors.lastname: de los Monteros
authors.forename: Ernesto
authors.initials: E
authors.lastname: Sosa
mesh_terms: D000172:Acromegaly / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I