CYP3A5基因的多态性及其临床意义的研究  

Study on polymorphisms of CYP3A5 gene and their clinical role

作　　者：王汉平[1] 谢健晋[1] 张泽云 应逸[1] 朱志刚[1] 毛平[1] 

机构地区：[1]广州市第一人民医院血液科,510180 [2]北京德博全基因检测技术研究所

出　　处：《中华医学遗传学杂志》2005年第4期423-426,共4页Chinese Journal of Medical Genetics

基　　金：广东省自然科学基金(04003652)~~

摘　　要：目的了解中国人群中细胞色素P4503A5基因CYP3A5的多态性及其基因型与临床功能之间的关联。方法应用变性高效液相色谱技术对180份样本进行基因变异的检测,并经测序验证;以免疫荧光偏振技术监测12例造血干细胞移植患者环孢素(cyclosporinA,CsA)血浓度,数据经统计学软件分析和处理。结果180份样本中,共检测出1种等位基因即CYP3A53,其频率为76.1%(274/360);3种基因型,即纯合子CYP3A51/110份,占总数的5.6%;杂合子CYP3A51/366份,占总数的36.7%;纯合子CYP3A53/3104份,占总数的57.8%。12例造血干细胞移植患者中检测出两种基因型,即CYP3A51/12例和CYP3A51/310例。CYP3A51/1患者外周血均一化后的CsA浓度与CYP3A51/3相比较,前者谷浓度C0较后者低,相差2.3～6.6倍,差异有统计学意义(P<0.01);服药后2h峰值C2亦较后者低,相差1.4～3.8倍,同样差异有统计学意义(P<0.01)。结论CYP3A53是中国人群中最主要的多态性,CYP3A5基因型与造血干细胞移植患者血中CsA浓度紧密关联,CYP3A51/1比CYP3A51/3需要更大剂量的CsA以维持相同的血浓度。应用变性高效液相色谱对CYP3A5进行基因型分型,可以预测患者CYP3A5的功能,进而预测其CsA的需求量,使临床应用CsA更加安全有效和个体化。Objective To investigate the polymorphisms of CYP3A5 gene in Chinese population and the association between CYF3A5 genotypes and their clinical functions. Methods CYP3A5 gene varisances were detected in 180 samples using denaturing high-performance liquid chromatography（DHPLC）, and CsA concentrations in 12 of 180 samples from hemopoietic stem cell transplant recipients were monitored by a cormmereial fluorescence polarization immunoassay. The data were analyzed by a statistical software. Results In the 180 samples, there was only one allelic variant CYP3A5 ＊ 3 with a frequency of 76.1% （274/360）, and there were threeCYP3A5 genotypes, namely CYP3A5 ＊ 1/＊ 1 ,CYP3A5 ＊ 1/＊ 3 and CYP3A5 ＊ 3/＊ 3 with frequencies of 5.6%, 36.7% and 57.8% respectively. Also, there were significant differences in CsA concentrations, including standardized trough concentrations C0 and two-hour peak concentrations C2, between CYP3A5 CYP3A5 ＊ 1/＊ 1 and CYP3A5 ＊ 1/＊ 3 found in 12 hemopoietic stem cell transplant recipients, and both C0 and C2 in CYP3A5 ＊ 1/＊ 1 were lower than those in CYP3A5 ＊ 1/＊ 3. Conclusion CYP3A5 ＊ 3 is the primary allelic variant in Chinese population. CYP3A5 genotypes are closely associated with blood CsA concentrations in hemopoietic stem cell transplant recipients, and CYP3A5 ＊ 1/＊ 1 requires a larger CsA dose to maintain the same blood concentration than does CYP3A5 ＊1/＊ 1. CYP3A5 genotyping by DHPLC may predict recipients＇ phenotype and CsA dose requirement.

关 键 词：CYP3A5基因 基因多态性 环孢素 基因型 高效液相色谱技术 

分 类 号：R394[医药卫生—医学遗传学]