广州地区318例拟应用伏立康唑治疗的疑似侵袭性真菌感染患者CYP2C19^(*)2/^(*)3/^(*)17等位基因检测分析  

Detection and analysis of CYP2C19^(*)2/^(*)3/^(*)17 allele in 318 patients with suspected invasive fungal infection to be treated with voriconazole in Guangzhou

作　　者：杨建良[1] 苏铎华[1] 李祥[1] 周晓雯[1] 植嘉玲 邢贞建[1] 钟洪兰[1] Yang Jianliang;Su Duohua;Li Xiang;Zhou Xiaowen;Zhi Jialing;Xing Zhenjian;Zhong Honglan(Department of Pharmacy,Guangzhou Chest Hospital,Guangzhou 510095,China)

机构地区：[1]广州市胸科医院药剂科,广州510095

出　　处：《国际医药卫生导报》2023年第9期1214-1217,共4页International Medicine and Health Guidance News

基　　金：广东省医学科学技术研究基金(B2022146)。

摘　　要：目的了解广州地区人群CYP2C19^(*)2/^(*)3/^(*)17等位基因9154G>A、7948G>A和806C>T位点的多态性,为临床应用伏立康唑治疗侵袭性真菌感染提供参考依据。方法选取2022年1月至2023年2月在广州市胸科医院就诊、拟应用伏立康唑治疗且进行CYP2C19^(*)2/^(*)3/^(*)17等位基因检测的318例疑似侵袭性真菌感染患者纳入分析,其中男249例、女69例,年龄19~94岁,平均58岁。应用数字荧光分子杂交测序技术检测CYP2C19^(*)2(9154G>A)、CYP2C19^(*)3(7948G>A)、CYP2C19^(*)17(806C>T)位点的多态性,描述性分析伏立康唑快、中、慢代谢型患者的基因型、单倍型分布频率。结果在CYP2C19^(*)2(9154G>A)位点上检测到GG、AG、AA 3种基因型,分布频率分别为47.80%(152/318)、42.45%(135/318)、9.75%(31/318);在CYP2C19^(*)3(7948G>A)位点上检测到GG、GA、AA 3种基因型,分布频率分别为90.88%(289/318)、8.81%(28/318)、0.31%(1/318);在CYP2C19^(*)17(806C>T)位点上检测到CC、CT 2种基因型,分布频率分别为99.37%(316/318)、0.63%(2/318)。318例拟应用伏立康唑治疗的患者中,快、中、慢代谢型的患者分别有135例(42.45%)、140例(44.03%)和43例(13.52%),3个基因位点单倍型情况为:GG-GG-GC、GG-GG-CT 2种快代谢单倍型,分布频率分别为99.26%(134/135)和0.74%(1/135);AG-GG-CC、GG-GA-CC、AG-GG-CT 3种中间代谢单倍型,分布频率分别为87.86%(123/140)、11.43%(16/140)和0.71%(1/140);AA-GG-CC、AG-GA-CC、AA-GA-CC、GG-AA-CC 4种中间代谢单倍型,分布频率分别为69.77%(30/43)、25.58%(11/43)、2.33%(1/43)和2.33%(1/43)。结论从CYP2C19基因遗传背景看,广州地区人群虽多为伏立康唑快、中代谢型,但慢代谢型占有一定比例,在临床诊疗中应重视其基因多态性检测,进而指导伏立康唑的临床合理应用。Objective To understand the polymorphisms of CYP2C19^(*)2/^(*)3/^(*)17 alleles 9154G>A,7948G>A,and 806C>T in Guangzhou population,and to provide reference for the clinical application of voriconazole in the treatment of invasive fungal infections.Methods A total of 318 patients with suspected invasive fungal infection who were scheduled to be treated with voriconazole and were tested for CYP2C19^(*)2/^(*)3/^(*)17 allele in Guangzhou Chest Hospital from January 2022 to February 2023 were selected for analysis,including 249 males and 69 females,aged 19-94 years(with a mean age of 58 years old).The polymorphism of CYP2C19^(*)2(9154G>A),CYP2C19^(*)3(7948G>A),and CYP2C19^(*)17(806C>T)in the patients was detected by digital fluorescence molecular hybridization sequencing.The distribution frequencies of genotypes and haplotypes in patients with fast,medium,and slow voriconazole metabolism types were analyzed.Results GG,AG,and AA genotypes were detected on the CYP2C19^(*)2(9154G>A)locus,with the distribution frequencies of 47.80%(152/318),42.45%(135/318),and 9.75%(31/318),respectively.GG,GA,and AA genotypes were detected on the CYP2C19^(*)3(7948G>A)locus,with the distribution frequencies of 90.88%(289/318),8.81%(28/318),and 0.31%(1/318),respectively.CC and CT genotypes were detected on the CYP2C19^(*)17(806C>T)locus,with the distribution frequencies of 99.37%(316/318)and 0.63%(2/318),respectively.In the 318 patients to be treated with voriconazole,there were 135(42.45%),140(44.03%),and 43(13.52%)patients with fast,medium,and slow voriconazole metabolism types,respectively.The haplotypes of the 3 gene loci were 2 fast metabolism haplotypes of GG-GG-GC and GG-GG-CT,with the distribution frequencies of 99.26%(134/135)and 0.74%(1/135),3 medium metabolism haplotypes of AG-GG-CC,GG-GA-CC,and AG-GG-CT,with the distribution frequencies of 87.86%(123/140),11.43%(16/140),and 0.71%(1/140),and 4 medium metabolism haplotypes of AA-GG-CC,AG-GA-CC,AA-GA-CC,and GG-AA-CC,with the distribution frequencies of 69.77%(30/43),25.58%(11/43),2.

关 键 词：基因多态性 细胞色素P450 CYP2C19基因 伏立康唑 数字荧光分子杂交测序技术 

分 类 号：R519[医药卫生—内科学] R440[医药卫生—临床医学]