Influence of Calcineurin Gene Polymorphisms on the Efficacy of Cyclosporine A
10.6039/j.issn.1001-0408.2016.29.01
- VernacularTitle:钙调神经磷酸酶基因多态性对环孢素A药效的影响
- Author:
Jing YAO
;
Yingmin HAI
;
Dingding CHEN
;
Weihong GE
;
Huaijun ZHU
- Publication Type:Journal Article
- Keywords:
Calcineurin;
CyclosporinA;
Individual administration;
Gene polymorphism
- From:
China Pharmacy
2016;27(29):4033-4036,4037
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the influence of calcineurin gene polymorphism on the efficacy of cyclosporine A (CsA). METHODS:The blood samples of patients treated with CsA were collected. The trough blood concentration of CsA was detected by EMIT. The genotype of PPP3CA and PPP3CB was assayed by RFLP-PCR method. The expression of NFAT-regulated gene IL-2, IFN-γand GM-CSF were measured by RT-qPCR,which were used to define the index of indirect efficacy of CsA. The relationship of gene polymorphism with CsA efficacy was study by relationship analysis and multiple factor regression method,etc. RESULTS:A to-tal of 100 blood samples were collected. There was no significant correlation between the expression of CsA efficacy-related NFAT-reg-ulated gene GM-CSF and trough concentration of CsA(rGM-CSF=-0.04,P=0.238);the expression of IL-2 and IFN-γ were negatively correlated with trough concentration of CsA significantly(rIL-2=-0.384 3,P<0.001;rIFN-γ=-0.335 4,P<0.001). Using the average value of mRNA expression of IL-2 and IFN-γas indirect efficacy index,the polymorphism of PPP3CB rs3763679 site significantly in-fluenced the efficacy of CsA(P<0.05),but PPP3CA rs3804358 had no any effect on it(P>0.05). Stratified analysis showed that among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 genovariation(TC+TT) were better than those with wild-type gene (CC)(P<0.05). After the efficacy was normalized by CsA trough concentration, multivariate analysis showed that normalized efficacy of CsA was negatively correlated with gender,PPP3CB rs3763679,lactate dehy-drogenase and creatinine significantly,but positively correlated with PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate,etc. CONCLUSIONS:PPP3CB rs3763679 gene polymorphism influence the efficacy of CsA;among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 TT+TC is better than that of CC type. At the same time,gender,PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate and other factors all can influence the nor-malized efficacy of CsA to different extent. Multiple factors should be considered when using CsA.
