title: Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.
abstract: OBJECTIVE
  Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
  
  
  METHODS
  Using a candidate gene approach, fifteen single-nucleotide polymorphisms (SNPs) in nine genes with known impact on renal tubular function (AGT, SCNN1A, SCNN1G, SLC12A1, SLC12A3, KCNJ1, STK39, WNK1 and CASR) were genotyped and analyzed for associations with ECW and BP at baseline and with their changes after 1 year of GHRT in 311 adult GHD patients. ECW was measured with the Br(-), BIA, and BIS.
  
  
  RESULTS
  Both BIA and BIS measurements demonstrated similar ECW results as the reference method. At baseline, after adjustment for sex and BMI, SNP rs2291340 in the SLC12A1 gene was associated with ECW volume in GHD patients (p = 0.039). None of the SNPs influenced the ECW response to GHRT. One SNP in the SLC12A3 gene (rs11643718; p = 0.024) and three SNPs in the SCNN1G gene [rs5723 (p = 0.02), rs5729 (p = 0.016) and rs13331086 (p = 0.035)] were associated with the inter-individual differences in BP levels at baseline. A polymorphism in the calcium-sensing receptor (CASR) gene (rs1965357) was associated with changes in systolic BP after GHRT (p = 0.036). None of these associations remained statistically significant when corrected for multiple testing.
  
  
  CONCLUSIONS
  The BIA and BIS are as accurate as Br(-) to measure ECW in GHD adults before and during GHRT. Our study provides the first evidence that individual polymorphisms may have clinically relevant effects on ECW and BP in GHD adults.
authors.affiliation: Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; SEMPR, Servico de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Edna J L
authors.initials: EJ
authors.lastname: Barbosa
authors.affiliation: Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Camilla A M
authors.initials: CA
authors.lastname: Glad
authors.affiliation: Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Nutrition Unit, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Bosaeus
authors.affiliation: Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helena Filipsson
authors.initials: HF
authors.lastname: Nyström
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.affiliation: Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Bengt-Åke
authors.initials: BÅ
authors.lastname: Bengtsson
authors.affiliation: Institute of Mathematical Sciences, Department of Mathematical Statistics, Chalmers University of Technology, Chalmers, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Nutrition Unit, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ingvar
authors.initials: I
authors.lastname: Bosaeus
authors.affiliation: SEMPR, Servico de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Cesar Luiz
authors.initials: CL
authors.lastname: Boguszewski
authors.affiliation: Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D001834:Body Water / Q000502:physiology*; D004393:Dwarfism, Pituitary / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045604:Extracellular Fluid / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone