The Role Of PIN1Gene Single Nucleotide Polymorphism In Chronic Kidney Disease

Background Peptidyl-prolyl cis/trans isomerase NIMA-interacting1(Pinl) is one of the peptide-prolyl isomerase family members. It is through specific catalytic Ser/Thr-pro amino acid motif to regulate the cell cycle protein conformation, and ultimately affect cell proliferation and differention. Recent studies have showed that Pin1is a key regulator of PTH mRNA stability. When Pin] reduced or its activity decreased, the PTH mRNA stability increased and degradation decreased, resulting in the elevated levels of serum parathyroid hormone (PTH). Secondary hyperparathyroidism is a common complication of CKD, which characterized by elevated serum PTH level. At present, the PIN1gene single nucleotide polymorphism (SNP) only sporadicly reported in tumor. However, the PIN1gene and Pin1concentration are related to the occurrence and development of CKD were all never reported. How the PIN1gene SNP to regulate the relationship of Pin1and PTH with CKD in urgent need of depth study.Objective1. To analyze the PIN1gene promoter region-667C>T genotypes and alletic frequencies in the control group and the different stages of CKD.2. To compare plasma Pinl and PTH concentration in the control group and the different stages of CKD, and to elucidate the relationship between plasma Pinl with PTH and the occurrence and development of CKD.3. To study the relationship between the different genotypes of the PIN1gene promoter region-667C>T and the plasma Pin1and PTH levels, and to discuss the PIN1gene promoter region-667C>T polymorphism on plasma Pin1and PTH concentration.Methods1. A total of252non-dialytic CKD patients in our hospital were enrolled in the study. The CKD group was divided into5stages in accordance with the2002K/DOQ1. At the same time.61healthy volunteers were enrolled as control.2. The polymorphism of PIN1gene was detected by using polymerase chain reaction-restriction (PCR) and restriction fragment length polymorphisma (RFLP).3. The polymorphism of PIN1gene was verificated by genome sequencing. 4. The plasma Pin1and PTH were detected by enzyme-linked immunosorbent assay (EL1SA).5. Statistical analysis by using SPSS17.0statistical software.Result1. The CKD group PIN1gene promoter region-667C>T genotypes and allelic frequencies comparison with the control group showed statistical significance (P＜0.05).-667T allele frequency was significantly higher than control group (P<0.05). It suggested that there was a relationship between PIN] gene promoter region-667C>T polymorphism and the occurrence of CKD,-667T mutant gene may be a susceptide factor for CKD.2. The PIN] gene promoter region-667C>T genotypes and allelic frequencies among the control group with the groups of CKD group were statistically significant (P＜0.05), but no statistical significance in the groups of CKD group. With the progress of CKD,-667T variant genotypes (CT and TT) and T allele frequency gradually increased, which showed PIN] gene promoter region-667C>T polymorphism is correlation with CKD progress.3. Pin] is a protective factor of CKD according to the analysis of the logistic forward stepwise multiple regression on multifactors such as sex and age (OR<1).4. The plasma Pin land PTH concentration of CKD group were significantly higher than that of control group (P＜0.05). With the progress of CKD, the plasma Pin1concentration was on a downward trend and PTH upward trend in turn, and statistically significant (PO.05).5. When the PIN1promoter region-667C>T genotypes were CC, CT and TT, not only the statistical significance showed among the overall plasma Pin1and PTH concentration, but also between any two of them (P＜0.05).Conclusion1. PIN1gene promoter region-667C>T polymorphism is related to the occurrence and development of CKD.-667T allele may be a susceptide factor for CKD.2. Pinl is one of the protective factors of CKD, which is related to the occurrence and development of CKD. As the progress of CKD, the plasma Pin1concentration decreases leading to the protective effect weakened.3. PIN1gene promoter region-667C>T polymorphism has an impact on plasma Pin1and PTH concentration.4. The plasma Pinl showed significant negative correlation with PTH. the Pin1plays an impotant role in the occurrence and development of CKD SHPT.