Correlationship between ATP binding cassette subfamily B member 1 2677G>T/A gene polymorphism and cyclosporine blood concentration in patients with autoimmune diseases
10.3760/cma.j.c141217-20201120-00440
- VernacularTitle:ABCB1 2677G>T/A基因多态性与自身免疫病患者环孢素A血药浓度个体差异的相关性研究
- Author:
Qing SHU
1
;
Yunxing LIU
;
Yonghan GE
;
Huaijun ZHU
;
Yao YAO
;
Hong WANG
;
Weihong GE
Author Information
1. 南京大学医学院附属鼓楼医院药学部 210008
- Keywords:
Polymorphism, single nucleotide;
Plasma concentration;
Autoimmune diseases;
Gene polymorphism
- From:
Chinese Journal of Rheumatology
2021;25(7):433-440
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the distribution of blood concentration of cyclosporine (CsA) in patients with autoimmune disease in China, and analyze the effect of genetic polymorphisms of CsA-metabolizing enzymes, transporters and target enzymes on CsA levels.Methods:Steady-state trough blood concentrations (CsA C 0) of 193 patients' were detected by enzyme multiplied immunoassay technique. The genotype of the following sites in the included patients were sequenced by reverse transcription-polymerase chain reaction (RT-PCR): cytochrome P450 (CYP) 3A420230C>T, CYP3A56986A>G, ATP binding cassette subfamily B member 1 (ABCB1)1236C>T, ABCB12677G>T/A, ABCB13435C>T, cytochrome P450 oxidoreductase (POR) 1508 C>T and formyl peptide receptor 1 (FPR1) C>G were sequenced by RT-PCR. The influence of the gene polymorphism of the above-mentioned sites on the blood concentration of CsA was analyzed by using One-way analysis of variance (ANOVA), LSD- t test, Chi-square test. Results:One hundred and ninety-three patients included took CsA. The doses ranged from 75-200 mg/d and the patients' blood concentration distribution span was wide (33.0-313.8 ng/ml). The daily dose ( χ2=21.908, P=0.001) and age( F=4.262, P=0.006) had significant effect on the plasma concentration of CsA. ABCB12677G>T/A (rs2032582) gene polymorphism impacted on the unit dose of CsA C 0 (CsA C 0/d), CsA C 0/d [(0.81±0.42) ng·ml -1·mg -1] in wild type (GG) was higher than heterozygous mutant [GT/GA, (0.65±0.30) ng·ml -1·mg -1, P=0.023) and homozygous mutant (TT/AA/TA, (0.66±0.34) ng·ml -1·mg -1, P=0.039). Conclusion:The blood concentration of patients varies greatly among individuals. The Cold of CsA in wild type patients with ABCB12677G>T/A gene is signifficantly higher than that in mutant patients.
