title: Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.
abstract: Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined.
  
  
  
  To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease.
  
  
  
  68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR.
  
  
  
  The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone.
  
  
  
  The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients.
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.|Lendület" Hereditary Endocrine Tumours Research Group, Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Molnár
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Kövesdi
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Nikolette
authors.initials: N
authors.lastname: Szücs
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Igaz
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.|Molecular Medicine Research Group, Semmelweis University - Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Rácz
authors.affiliation: Lendület" Hereditary Endocrine Tumours Research Group, Budapest, Hungary.|Molecular Medicine Research Group, Semmelweis University - Hungarian Academy of Sciences, Budapest, Hungary.|Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Patócs
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000224:Addison Disease / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D015430:Weight Gain
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human