中华结核和呼吸杂志
中華結覈和呼吸雜誌
중화결핵화호흡잡지
Chinese Journal of Tuberculosis and Respiratory Diseases
2011年
5期
362-366
,共5页
蔡畅%周美茜%李玉苹%陈成水
蔡暢%週美茜%李玉蘋%陳成水
채창%주미천%리옥평%진성수
哮喘%白三烯类%多态性,单核苷酸%孟鲁司特
哮喘%白三烯類%多態性,單覈苷痠%孟魯司特
효천%백삼희류%다태성,단핵감산%맹로사특
Asthma%Leukotrienes%Polymorphism,single nucleotide%Montelukast
目的 检测温州地区汉族人支气管哮喘(简称哮喘)患者白三烯酶基因多态性的分布频率,探讨酶基因多态性与孟鲁司特治疗的相关性.方法 采用基质辅助激光解吸附电离飞行时间质谱法,对60例温州汉族哮喘患者(哮喘组)及61名健康者(对照组)的6个白三烯酶基因多态性位点进行检测.依据基因检测结果选取基因白三烯C4合成酶LTC4S(rs730012)CC+AC型11例与从型11例,观察孟鲁司特治疗4周后的肺功能和尿白三烯E4的变化.结果 (1)6个基因位点[5脂氧酶ALOX5(rs2115819、rs4986832、rs4987105)、白三烯A4水解酶LTA4H(rs2660845)、5脂氧酶结合蛋白ALOX5AP(rs10507391)和LTC4S(rs730012)]的变异频率均＜50%,单体型组间分布差异均无统计学意义(均P＞0.05).(2)基因ALOX5(rs2115819、rs4986832、rs4987105)和LTA4H(rs2660845)等位点变异等位基因频率组间比较差异均无统计学意义(OR值分别为1.1 12、0.964、0.964、0.673,均P＞0.05),变异等位基因OR值95%可信区间(95%CI)均包括无效值(OR=1.0).上述位点基因型组间比较差异均无统计学意义(χ2值分别为0.792、2.684、2.683、2.524,均P＞0.05).(3)基因ALOX5AP(rs10507391)位点在两组间存在差异,哮喘组变异等位基因A频率为23.3%(OR=2.016,95%CI为1.027～3.959,P＜0.05).基因LTC4S(rs730012)位点在两组间存在差异,哮喘组变异等位基因C频率为25.0%(OR=1.926,95%CI为1.007～3.685,P＜0.05).(4)孟鲁司特治疗4周后,基因LTC4S(rs730012)CC+AC型者的FEVl提高(t=6.185,P＜0.01),晨尿LTE4下降(t=2.925,P＜0.05).AA型者治疗前后的FEV,和LTE4无明显变化.结论 温州地区汉族人群中基因ALOX5AP(rs10507391)、LTC4S(rs730012)位点的变异与哮喘相关,而另外4个位点的变异与哮喘无关.携带LTC4S(rs730012)变异等位基因C型可影响孟鲁司特的治疗效应.
目的 檢測溫州地區漢族人支氣管哮喘(簡稱哮喘)患者白三烯酶基因多態性的分佈頻率,探討酶基因多態性與孟魯司特治療的相關性.方法 採用基質輔助激光解吸附電離飛行時間質譜法,對60例溫州漢族哮喘患者(哮喘組)及61名健康者(對照組)的6箇白三烯酶基因多態性位點進行檢測.依據基因檢測結果選取基因白三烯C4閤成酶LTC4S(rs730012)CC+AC型11例與從型11例,觀察孟魯司特治療4週後的肺功能和尿白三烯E4的變化.結果 (1)6箇基因位點[5脂氧酶ALOX5(rs2115819、rs4986832、rs4987105)、白三烯A4水解酶LTA4H(rs2660845)、5脂氧酶結閤蛋白ALOX5AP(rs10507391)和LTC4S(rs730012)]的變異頻率均＜50%,單體型組間分佈差異均無統計學意義(均P＞0.05).(2)基因ALOX5(rs2115819、rs4986832、rs4987105)和LTA4H(rs2660845)等位點變異等位基因頻率組間比較差異均無統計學意義(OR值分彆為1.1 12、0.964、0.964、0.673,均P＞0.05),變異等位基因OR值95%可信區間(95%CI)均包括無效值(OR=1.0).上述位點基因型組間比較差異均無統計學意義(χ2值分彆為0.792、2.684、2.683、2.524,均P＞0.05).(3)基因ALOX5AP(rs10507391)位點在兩組間存在差異,哮喘組變異等位基因A頻率為23.3%(OR=2.016,95%CI為1.027～3.959,P＜0.05).基因LTC4S(rs730012)位點在兩組間存在差異,哮喘組變異等位基因C頻率為25.0%(OR=1.926,95%CI為1.007～3.685,P＜0.05).(4)孟魯司特治療4週後,基因LTC4S(rs730012)CC+AC型者的FEVl提高(t=6.185,P＜0.01),晨尿LTE4下降(t=2.925,P＜0.05).AA型者治療前後的FEV,和LTE4無明顯變化.結論 溫州地區漢族人群中基因ALOX5AP(rs10507391)、LTC4S(rs730012)位點的變異與哮喘相關,而另外4箇位點的變異與哮喘無關.攜帶LTC4S(rs730012)變異等位基因C型可影響孟魯司特的治療效應.
목적 검측온주지구한족인지기관효천(간칭효천)환자백삼희매기인다태성적분포빈솔,탐토매기인다태성여맹로사특치료적상관성.방법 채용기질보조격광해흡부전리비행시간질보법,대60례온주한족효천환자(효천조)급61명건강자(대조조)적6개백삼희매기인다태성위점진행검측.의거기인검측결과선취기인백삼희C4합성매LTC4S(rs730012)CC+AC형11례여종형11례,관찰맹로사특치료4주후적폐공능화뇨백삼희E4적변화.결과 (1)6개기인위점[5지양매ALOX5(rs2115819、rs4986832、rs4987105)、백삼희A4수해매LTA4H(rs2660845)、5지양매결합단백ALOX5AP(rs10507391)화LTC4S(rs730012)]적변이빈솔균＜50%,단체형조간분포차이균무통계학의의(균P＞0.05).(2)기인ALOX5(rs2115819、rs4986832、rs4987105)화LTA4H(rs2660845)등위점변이등위기인빈솔조간비교차이균무통계학의의(OR치분별위1.1 12、0.964、0.964、0.673,균P＞0.05),변이등위기인OR치95%가신구간(95%CI)균포괄무효치(OR=1.0).상술위점기인형조간비교차이균무통계학의의(χ2치분별위0.792、2.684、2.683、2.524,균P＞0.05).(3)기인ALOX5AP(rs10507391)위점재량조간존재차이,효천조변이등위기인A빈솔위23.3%(OR=2.016,95%CI위1.027～3.959,P＜0.05).기인LTC4S(rs730012)위점재량조간존재차이,효천조변이등위기인C빈솔위25.0%(OR=1.926,95%CI위1.007～3.685,P＜0.05).(4)맹로사특치료4주후,기인LTC4S(rs730012)CC+AC형자적FEVl제고(t=6.185,P＜0.01),신뇨LTE4하강(t=2.925,P＜0.05).AA형자치료전후적FEV,화LTE4무명현변화.결론 온주지구한족인군중기인ALOX5AP(rs10507391)、LTC4S(rs730012)위점적변이여효천상관,이령외4개위점적변이여효천무관.휴대LTC4S(rs730012)변이등위기인C형가영향맹로사특적치료효응.
Objective To investigate the frequencies of leukotriene gene single nucleotide polymorphisms(SNPs)in the asthmatic subiects of Han population in Wenzhou district,and the association between SNPs and response to montelukast treatment. Methods Sequenom matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF)was used to genotype six polymorphisms in 60 asthmatic patients and 61 controls.According to the SNPs results,11 cases with the LTC4S(rs730012)CC+AC genotype and 11subjects with the AA genotype were given montelukast treatment,and evaluated by the response of pulmonary function and urinary leukotriene E4.Results The frequencies of mutant SNPs in ALOX5(rs2115819,rs4986832,r94987105),LTA4H(rs2660845),ALOX5AP(rsl0507391)and LTC4S (rs730012)were less than 50%.There were no statistical differences of the haplotype distribution (P values were 0.914,0.609.0.609,0.315.0.752 and 0.636 respectively).No statistical difireFences of the mutant allele frequencies were observed in the genes ALOX5(rs2115819,rs4986832,rs4987105)and LTA4H(rs2660845)(OR values were 1.112,0.964,0.964 and 0.673 respectively,all P＞0.05).The invalid value(OR=1.0)was included in the 95%CI of odds ratios.There were no differences of genotype distribution in the above loci(χ2 values were 0.792,2.684,2.683 and 2.524 respectively,all P＞0.05).There was a statistical difierence in the ALOX5 AP(rs10507391)mutant allele between the 2 groups,and the frequency of mutant alllele A in the asthma group was 23.3%(OR=2.016,95%CI=1.027-3.959,P<0.05).There was a statistical difference in the LTC4S(rs730012)mutant allele between the 2 groups, and the frequency of the mutant allele C in the asthma group was 25.0%(OR=1.926.95%CI=1.007-3.685,P＜0.05).Compared with the AA genotype,the LTC4S(rs730012)CC+AC genotype showed a significant improvement of FEV1(t=6.185,P＜0.01)and urinary LTE4 level(t=2.925,P<0.05)after receiving montelukast treatment. Conclusions These results suggest that the SNPs of ALOX5 AP (rs10507391)and LTC4S(rs730012)are associated with asthma in our patients.The LTC4S(rs730012)locus genetic polymorphism contributes to improvement in montelukast response.
