title: Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene polymorphisms and protein levels.
abstract: BACKGROUND
  Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which is characterized by elevated serum PTH levels, is a common complication of CKD. We investigated the possible associations between CKD with SHPT (CKD SHPT) and single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the Pin1 protein in the CKD SHPT patients with those of the controls.
  
  
  METHODS
  The study group included 251 CKD SHPT patients and 61 controls. One putative functional SNP (single nucleotide polymorphism) in the Pin1 promoter (rs2233679C > T: c.-667C > T) is the main object. Genotyping was performed on purified DNA using polymerase chain reaction-restriction (PCR) and restriction fragment length polymorphisms (RFLP). The levels of Pin1 were measured in serum using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Genotyping showed that CT + TT in the Pin1 promoter was significantly more common in the CKD SHPT group than in the control group (p<.05). The correlation analysis demonstrated that a significant difference in the C to T transition in the Pin1 promoter contributed to CKD SHPT (χ2=12.47, p<.05; Odds ratios (OR) = 1.26, 95% confidence (CI) intervals =1.06-1.49). The multivariate logistic regression analysis reported that the OR and 95%CI were 12.693 and 2.029-75.819 (p<.05), respectively, in the Pin1 gene promoter -667T variant genotypes (CT + TT) after adjusting for other factors, and those values in Pin1 were 0.310 and 0.122-0.792 (p<.05).
  
  
  CONCLUSIONS
  The -667T genetic variants in the Pin1 promoter contribute to an increased risk of CKD SHPT and may be biomarkers of susceptibility to CKD SHPT.
authors.affiliation: a Department of Medicine , Northwest University for Nationalities , Lanzhou , PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: b Department of Nephrology , Second Hospital Affiliated of Lanzhou University , Lanzhou , PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: b Department of Nephrology , Second Hospital Affiliated of Lanzhou University , Lanzhou , PR China.
authors.forename: Fa-Xian
authors.initials: FX
authors.lastname: Ding
authors.affiliation: b Department of Nephrology , Second Hospital Affiliated of Lanzhou University , Lanzhou , PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Cao
authors.affiliation: b Department of Nephrology , Second Hospital Affiliated of Lanzhou University , Lanzhou , PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Qi
authors.affiliation: b Department of Nephrology , Second Hospital Affiliated of Lanzhou University , Lanzhou , PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012307:Risk Factors
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human
keywords: Chronic kidney disease; peptidyl-prolyl cis/trans isomerase NIMA-interacting 1; secondary hyperparathyroidism; single nucleotide polymorphism