目的 探討廣東省肇慶地區(qū)人群華法林相關(guān)基因細(xì)胞色素P450復(fù)合物亞基2C9（CYP2C9）和維生素K環(huán)氧還原酶復(fù)合物亞基1（VKORC1）多態(tài)性分布，并比較性別和中國(guó)西雙版納傣族、北京漢族、南方漢族間差異性的分布，為臨床醫(yī)生精準(zhǔn)使用華法林進(jìn)行抗凝治療提供理論基礎(chǔ)。方法 選取2019年5月-2022年1月于肇慶市第一人民醫(yī)院進(jìn)行華法林相關(guān)基因檢測(cè)的患者122例，所有患者均采用數(shù)字熒光分子雜交技術(shù)對(duì)CY92C9^*3和VKORC1進(jìn)行基因多態(tài)性檢測(cè)，比較患者性別間和中國(guó)西雙版納傣族、北京地區(qū)漢族、南方地區(qū)漢族間的基因多態(tài)性分布情況，并對(duì)比基于藥物基因組學(xué)指導(dǎo)下的華法林使用劑量與常規(guī)劑量使用華法林治療后2~3 d后國(guó)際標(biāo)準(zhǔn)化比值（INR）達(dá)標(biāo)率。結(jié)果 122例檢測(cè)樣本中，CY92C9^*3基因位點(diǎn)AA、AC、CC基因型所占的比例分別為95.90%、4.10%、0，C等位基因和T等位基因頻率分別為97.95%和2.05%；VKORC1基因位點(diǎn)GG、GA、AA基因型分別為0.82%、19.67%、79.51%，A等位基因和C等位基因頻率分別為10.66%和89.34%。不同性別間CY92C9^*3與VKORC1的基因型分布和等位基因分布差異均無統(tǒng)計(jì)學(xué)意義（P>0.05）。通過已有的數(shù)據(jù)庫(kù)進(jìn)行對(duì)比，肇慶地區(qū)的CY92C9^*3基因型、等位基因與1000 Genomes Project （1000 GP）西雙版納傣族、北京漢族與南方漢族對(duì)比無統(tǒng)計(jì)學(xué)差異（P>0.05）；但與1000 GP北京漢族對(duì)比，VKORC1的基因型和等位基因頻率有統(tǒng)計(jì)學(xué)差異（P<0.05）；與1000GP西雙版納傣族對(duì)比，VKORC1的等位基因頻率有統(tǒng)計(jì)學(xué)差異（P<0.05）；華法林在基因組學(xué)指導(dǎo)下的劑量與常規(guī)劑量治療后INR達(dá)標(biāo)率差異有統(tǒng)計(jì)學(xué)意義（P<0.01）。結(jié)論 肇慶地區(qū)人群存在CY92C9^*3和VKORC1基因多態(tài)性，其中VKORC1基因可能存在地域的差異，進(jìn)行華法林相關(guān)基因檢測(cè)可以為臨床制定個(gè)體化華法林抗凝方案提供重要的參考價(jià)值。

Objective To investigate the polymorphism distribution of warfarin-related genes CY92C9^*3 and VKORC1 in Zhaoqing area of Guangdong province, and to compare the distribution of gender differences and differences among Dai nationality in Xishuangbanna, Han nationality in Beijing and Han nationality in southern China, so as to provide a theoretical basis for clinicians to accurately use warfarin for anticoagulant therapy.Methods A total of 122 patients who underwent warfarin-related gene detection in Zhaoqing First People's Hospital from May 2019 to January 2022 were selected.All patients were tested for gene polymorphism of CY92C9^*3 and VKORC1 by digital fluorescence molecular hybridization.The distribution of gene polymorphisms between genders and among Dai nationality in Xishuangbanna, Han nationality in Beijing and Han nationality in southern China were compared, and the INR compliance rate of 2-3 days of warfarin treatment guided by pharmacogenomics was compared with that of conventional warfarin treatment.Results In 122 samples, the proportions of AA, AC and CC genotype of CY92C9^*3 locus were 95.90%, 4.10% and 0, respectively, and the frequencies of C allele and T allele were 97.95% and 2.05%, respectively.GG, GA and AA genotypes of VKORC1 were 0.82%, 19.67% and 79.51%, respectively.The frequencies of A allele and C allele were 10.66% and 89.34%, respectively.There were no significant differences in genotype and allele distribution of CY92C9^*3 and VKORC1 between different genders(P> 0.05).There was no significant difference in CY92C9^*3 genotype and allele between Zhaoqing and 1000 GP Dai nationality of Xishuangbanna, Han nationality of Beijing and Han nationality of south China(P> 0.05).However, there were significant differences in genotype and allele frequency of VKORC1 compared with 1000 GP Beijing Han(P<0.05).And there was significant differences in allele frequency of VKORC1 compared with 1000 GP Dai nationality of Xishuangbanna(P<0.05).The INR compliance rate of warfarin under the guidance of genomics was significantly different from that of conventional treatment(P<0.05).Conclusion CY92C9^*3 and VKORC1 gene polymorphisms exist in Zhaoqing population, among which VKORC1 gene may have regional differences, and warfarin-related gene detection can provide important reference value for clinical development of individual warfarin anticoagulation program.

R973

廣東省醫(yī)學(xué)科學(xué)技術(shù)研究基金（B2020133）；肇慶市科技創(chuàng)新指導(dǎo)類項(xiàng)目（2021040314010）