湖南省汉族肾移植受者CYP3A5基因及MDR-1基因的分布

Gene polymorphisms of CYP3A5 and MDR-1 in Hans renal transplant recipients in Hunan Province

目的:了解湖南省汉族肾移植人群中细胞色素P4503A5基因(cytochromeP4503A5,CYP3A5)与多药耐药基因1(multidrug resistance gene 1,MDR-1)的多态性分布情况,并分析与中国其他11省份汉族肾移植受者是否存在差异。方法:收集在中南大学湘雅三医院行肾移植手术及复诊的598例来自湖南省的汉族肾移植受者的血液样本进行基因检测,并经测序验证,然后与中国其他11省份汉族肾移植受者基因多态性的分布进行两独立样本的检验。结果:湖南省汉族肾移植受者CYP3A5*1/*1型为58例(9.7%),CYP3A5*1/*3型为251例(42.0%),CYP3A5*3/*3型为289例(48.3%);MDR-1 3435CC型为238例(39.8%),MDR-1 3435CT型为263例(44.0%),MDR-1 3435T型为97例(16.2%)。湖南省汉族肾移植受者CYP3A5*1/*1和*1/*3频率较全国其他11省份高,且突变基因*3频率较全国其他11省份低;MDR-1 3435CC和3435CT较全国其他11省份高,且突变基因T频率较全国其他11省份低。结论:湖南地区的汉族肾移植受者CYP3A5及MDR-1基因多态性分布及基因变异频率与中国其他11省份汉族肾移植受者有明显的差异,这对肾移植术后初期的钙调磷酸酶抑制剂类药物的应用具有一定指导意义。

Objective： To identify the polymorphisms of cytochrome P450 3A5 gene （CYP3A5） and multidrug resistance gene 1 （MDR-1） and their distributions in Hans renal transplant recipients in Hunan province, we analyzed the difference of the gene polymorphisms and distributions between Hunan province and 11 other provinces of China. Methods： We collected 598 Hans renal transplant recipients who had operation or follow-up examination in 3rd Xiangya Hospital from Hunan province. We examined the gene polymorphisms of CYP3A5 and MDR- 1 and compared their distributions with the data from 11 other provinces of China by chi-square test.Results： There were CYP3AS＊1/＊1 genotype in 58 cases （9.7%）, CYP3A5＊1/＊3 genotype in 251 cases （42.0%）, CYP3A5＊3/＊3 genotype in 289 cases （48.3%）; MDR-1 3435CC genotype in 238 cases （39.8%）, MDR-1 3435CT genotype in 263 cases （44.0%）, MDR-1 3435TT genotype in 97 cases （16.2%）. Frequency of CYP3A5＊1/＊1 and ＊1/＊3 genotypes of Hunan province was higher than the that from the 11 other provinces of China and the frequency of mutator ＊3 was lower. Frequency of MDR-1 3435CC and 3435CT genotypes of Hunan province was higher and the frequency of mutator T was lower than that from the 11 other provinces of China. Conclusions： There were significant difference in gene polymorphisms and distributions of CYP3A5 and MDR-1 between Hunan province and the 11 other provinces of China. It may be a guideline for us to use calcineurin inhibitor drugs in the early stage after renal transplantation.