中华内科杂志
中華內科雜誌
중화내과잡지
CHINESE JOURNAL OF INTERNAL MEDICINE
2012年
7期
524-530
,共7页
吴雪琼%朱冬林%张俊仙%钟逾%席云%安慧茹%梁艳%阳幼荣
吳雪瓊%硃鼕林%張俊仙%鐘逾%席雲%安慧茹%樑豔%暘幼榮
오설경%주동림%장준선%종유%석운%안혜여%량염%양유영
结核%肝损害%羧酸酯酶基因1%基因多态性
結覈%肝損害%羧痠酯酶基因1%基因多態性
결핵%간손해%최산지매기인1%기인다태성
Tuberculosis%Hepatotoxicity%Carboxylesterase 1%Genetic polymorphism
目的 研究羧酸酯酶(CES)基因1多态性及其与抗结核药物肝毒性易感性之间的关系.方法 应用PCR-时间飞行质谱技术(PCR-MassArray)分析473例抗结核治疗后发生肝损害(200例)和未发生肝损害(273例)结核病患者的CES1基因多态性,并通过统计学分析CES1各单核苷酸多态性(SNP)位点基因型与抗结核药物所致肝毒性之间的关系.结果 在筛选出的4个CES1标签SNP位点中,rs1968753的等位基因频率在肝损害和无肝损害组间存在分布差异(P=0.0236).SNP1rs8192950(P=0.044,OR=0.649,95％CI=0.426～0.989,AC/AA)和SNP2 rs1968753(P=0.048,OR =0.556,95％CI =0.311 ～0.995,GG/AA)与抗肝毒特性有显著关联.由‘CGC’参与构成的双单体型,在1份拷贝时表现出显著的肝毒保护性(P =0.048,OR=0.654,95％ CI=0.430～0.996).结论 CES1基因多态性可能与抗结核药物性肝损害密切相关,SNP rs8192950的AC基因型和rs1968753的GG基因型可能成为抗结核药物肝毒性风险预测的候选突变.
目的 研究羧痠酯酶(CES)基因1多態性及其與抗結覈藥物肝毒性易感性之間的關繫.方法 應用PCR-時間飛行質譜技術(PCR-MassArray)分析473例抗結覈治療後髮生肝損害(200例)和未髮生肝損害(273例)結覈病患者的CES1基因多態性,併通過統計學分析CES1各單覈苷痠多態性(SNP)位點基因型與抗結覈藥物所緻肝毒性之間的關繫.結果 在篩選齣的4箇CES1標籤SNP位點中,rs1968753的等位基因頻率在肝損害和無肝損害組間存在分佈差異(P=0.0236).SNP1rs8192950(P=0.044,OR=0.649,95％CI=0.426～0.989,AC/AA)和SNP2 rs1968753(P=0.048,OR =0.556,95％CI =0.311 ～0.995,GG/AA)與抗肝毒特性有顯著關聯.由‘CGC’參與構成的雙單體型,在1份拷貝時錶現齣顯著的肝毒保護性(P =0.048,OR=0.654,95％ CI=0.430～0.996).結論 CES1基因多態性可能與抗結覈藥物性肝損害密切相關,SNP rs8192950的AC基因型和rs1968753的GG基因型可能成為抗結覈藥物肝毒性風險預測的候選突變.
목적 연구최산지매(CES)기인1다태성급기여항결핵약물간독성역감성지간적관계.방법 응용PCR-시간비행질보기술(PCR-MassArray)분석473례항결핵치료후발생간손해(200례)화미발생간손해(273례)결핵병환자적CES1기인다태성,병통과통계학분석CES1각단핵감산다태성(SNP)위점기인형여항결핵약물소치간독성지간적관계.결과 재사선출적4개CES1표첨SNP위점중,rs1968753적등위기인빈솔재간손해화무간손해조간존재분포차이(P=0.0236).SNP1rs8192950(P=0.044,OR=0.649,95％CI=0.426～0.989,AC/AA)화SNP2 rs1968753(P=0.048,OR =0.556,95％CI =0.311 ～0.995,GG/AA)여항간독특성유현저관련.유‘CGC’삼여구성적쌍단체형,재1빈고패시표현출현저적간독보호성(P =0.048,OR=0.654,95％ CI=0.430～0.996).결론 CES1기인다태성가능여항결핵약물성간손해밀절상관,SNP rs8192950적AC기인형화rs1968753적GG기인형가능성위항결핵약물간독성풍험예측적후선돌변.
Objective To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CESI) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).Methods Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200∶ 273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.Results In4 tags of CES1 single nucleotide polymorphism (SNP),the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group ( P =0.0236 ).The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 ( P =0.044,OR =0.649,95％ CI =0.426-0.989,AC/AA ) and rs1968753 ( P =0.048,OR =0.556,95％ CI =0.311-0.995,GG/AA).The diplotypes with ‘ CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P=0.048,OR=0.654,95％CI=0.430-0.996).Conclusions The genetic polymorphisms of CESI might have significant association with ATBDIH.SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.
