title: Pharmacogenetic analysis of cinacalcet response in secondary hyperparathyroidism patients.
abstract: BACKGROUND
  Secondary hyperparathyroidism (SHPT) is one of the major risk factors of morbidity and mortality in end-stage renal disease. Cinacalcet effectively controls SHPT without causing hypercalcemia and hyperphosphatemia. However, there is significant inter-individual response variance to cinacalcet treatment. Therefore, we aimed to evaluate the genetic effects related with parathyroid hormone regulation as factors for cinacalcet response variance.
  
  
  METHODS
  Patients with a diagnosis of SHPT based on intact parathyroid hormone (iPTH) >300 pg/mL on dialysis were included in this study. They were over 18 years and have been treated by cinacalcet for more than 3 months. Responders and nonresponders were grouped by the serum iPTH changes. Twenty-four single nucleotide polymorphisms of CASR, VDR, FGFR1, KL, ALPL, RGS14, NR4A2, and PTHLH genes were selected for the pharmacogenetic analysis.
  
  
  RESULTS
  After adjusting for age, sex, and calcium level, CASR rs1042636 (odds ratio [OR]: 0.066, P=0.027) and rs1802757 (OR: 10.532, P=0.042) were associated with cinacalcet response. The association of haplotypes of CASR rs1042636, rs10190, and rs1802757; GCC (OR: 0.355, P=0.015); and ATT (OR: 2.769, P=0.014) with cinacalcet response was also significant.
  
  
  CONCLUSIONS
  We obtained supporting information of the associations between cinacalcet response and CASR polymorphisms. CASR single nucleotide polymorphisms (SNPs) rs1802757, rs1042636, and haplotypes of rs1042636, rs10190, and rs1802757 were significantly associated with cinacalcet response variance.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University.
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kook-Hwan
authors.initials: KH
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Oh
mesh_terms: D000328:Adult; D000368:Aged; D000069449:Cinacalcet / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D011110:Polymorphism, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D000069449:Cinacalcet
keywords: CASR; SHPT; calcium sensing receptor; genetic polymorphisms; haplotype; single nucleotide polymorphisms