血清白三烯B4水平与AMI发病风险和ALOX5AP基因SG13S114T/A多态性的相关性

目的:探讨中国苏南地区汉族人群血清白三烯(LT)B4水平与急性心肌梗死(AMI)发病风险和花生四烯酸5-脂氧合酶激活蛋白(ALOX5AP)基因SG13S114T/A多态性的相关性。方法:采用酶联免疫吸附试验和聚合酶链反应-限制性片段长度多态性方法对262例AMI患者(AMI组)和132例非冠心病者(对照组)分别检测血清LTB4水平(M/IQR)和ALOX5AP基因SG13S114T/A多态性。结果:AMI组和对照组均存在ALOX5AP基因SG13S114T/A多态性。血清LTB4水平在AMI组(477.97/370.52ng·L-1)明显高于对照组(200.57/236.65ng·L-1)(P0.01),与吸烟呈正相关(P0.01,R2=0.039),与性别、年龄、高血压、糖尿病和血脂异常均无关。AMI组ALOX5AP基因SG13S114位点AA、AT和TT任何基因型之间的血清LTB4水平均无显著差异(517.98/392.00ng·L-1∶492.31/427.55ng·L-1∶495.29/398.54ng·L-1),在同性别AMI亚组中亦无明显差异。结论:中国苏南地区汉族人群血清LTB4水平明显升高,并与AMI发病风险相关,但与ALOX5AP基因SG13S114多态性无相关性。     

血清白三烯B4水平、ALOX5AP基因SG13S89G/A多态性与急性心肌梗死的关联性研究

目的:探讨中国常州地区汉族人群血清白三烯(LT)B4水平、花生四烯酸5-脂氧合酶激活蛋白(ALOX5AP)基因SG13S89G/A多态性和急性心肌梗死(AMI)三者的相互关联性。方法:以262例AMI患者(AM I组)和132例非冠心病患者(对照组)作为研究对象,采用聚合酶链反应-限制性片段长度多态性方法检测ALOX5AP基因SG13S89G/A多态性,同时采用酶联免疫吸附试验检测血清LTB4水平(以中位数/四分位数间距表示)。结果:对照组与AMI组ALOX4AP基因SG13S89G/A位点的(AA+GA)基因型(7.58%︰4.96%)、GG基因型(92.42%︰95.04%)以及A等位基因(4.17%︰2.67%)频率均差异无统计学意义;多变量Logistic回归分析显示,该位点多态性与AMI发病风险无显著相关性;AMI组血清LTB4水平显著高于对照组(477.97/370.52pg/ml︰200.57/236.65pg/ml,P<0.01);多变量Logistic回归分析显示,血清LTB4水平与AMI发病风险有显著相关性(P<0.01);AMI组和对照组的组内(AA+GA)基因型和GG基因型之间的血清LTB4水平比较差异无统计学意义。结论:中国常州地区汉族人群AMI患者血清LTB4水平显著升高,ALOX5AP基因SG13S89G/A多态性与AMI易感性无关,且不影响血清LTB4水平。     

心肌梗死患者ALOX5AP基因SG13S114T/A和SG13S89G/A多态性研究

目的探讨中国汉族人群中的ALOXSAP基因SG13S114T/A和SG13S89G/A多态性与心肌梗死的关系。方法应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对95例急性心肌梗死(AMI)患者和114名健康对照者外周血提取的DNA样本,进行SG13S114T/A和SG13S89G/A点突变分析,对突变型进行DNA测序验证。结果 SG13S114T/A及SG13S89G/A单核苷酸多态位点基因频率在AMI组和对照组与HapMap报道数据差异无统计学意义。基因多态性与心肌梗死发病情况的相关情况:SG13S114A/A(OR=1.264,95%可信区间:0.637～2.510,P=0.45):SG13S114A/T(OR=1.127,95%可信区间:0.670～1.897,P=0.20);SG13S114T/T(OR=0.745,95%可信区间:0.424～1.311,P=1.04)。结论无显著证据表明ALOX5AP基因SG13S114T/A和SG13S89G/A多态性与心肌梗死发病风险有密切相关性。     

花生四烯酸5-脂氧合酶激活蛋白基因多态性与急性冠状动脉综合征的易感性

目的探讨花生四烯酸5脂氧合酶激活蛋白(ALOX5AP)基因SG1 3S114T/A多态性与急性冠状动脉综合征(ACS)的易感性。方法选择住院的胸痛患者714例,将确诊为ACS的患者377例作为ACS组,非ACS患者337例作为对照组,采用聚合酶链反应限制性片段长度多态性方法检测ALOX5AP基因SG13S114T/A多态性,并进行logistic回归分析。结果 ACS组患者AA、AT和TT基因型频率分别为1 3.79%、50.93%和35.28%,对照组患者分别为12.76%、38.58%和48.66%,2组AT和TT基因型频率差异有统计学意义(P=0.041,0.020);ACS组男性AT基因型频率高于对照组(P=0.040),女性TT基因型频率低于对照组(P=0.013)。SG13S114T/A位点AT和TT基因型以及T等位基因是所有ACS(P=0.004、0.001和0.013)和男性ACS(P=0.014、0.005和0.020)发病的危险因素。结论 ALOX5AP基因SG1 3S114T/A多态性AT和TT基因型以及T等位基因可能与老年人,特别是老年男性ACS的易感性相关。     

5-脂氧合酶激活蛋白基因多态性增加阿司匹林抵抗易感性

目的探讨5-脂氧合酶激活蛋白(ALOX5AP)基因单核苷酸多态性与中国汉族人群阿司匹林抵抗(AR)的相关性。方法纳入450例持续服用阿司匹林(100mg,≥7d)的缺血性心脑血管病中的高危患者,血栓弹力图检测花生四烯酸途径的血小板聚集率,依据诊断标准分为AR组110例,阿司匹林敏感(AS)组340例。聚合酶链反应-限制性片段长度多态性技术分析SG13S32、SG13S89和SG13S114单核苷酸多态性。应用Haploview软件构建单倍型,并进行分析。结果 AR组与AS组SG13S114T/A突变A等位基因频率分布(40.5%vs 31.3%,P=0.01)和AA/TA基因型及TT基因型比较,差异有统计学意义(35.5%vs 46.2%,P=0.03)。而2组SG13S89、SG13S32基因型和等位基因分布频率比较,差异无统计学意义(P0.05)。logistic回归分析显示,携带SG13S114AA/TA基因型的人群发生AR的风险是携带TT基因型的3.241倍(95%CI:1.552~6.767,P=0.002)。单倍型分析显示,TG是1种危险单倍型,携带TG单倍型的人群AR发生风险是不携带TG单倍型人群的1.490倍(95%CI:1.088~2.040,P=0.014),AG是1种保护单倍型,可以减少AR发生的风险(OR=0.691,95%CI:0.502~0.952,P=0.029)。结论 ALOX5AP rs10507391与汉族人群AR相关;危险单倍型TG可增加AR发生风险。     

浙江南部地区人群5-脂氧合酶激活蛋白和磷酸二酯酶4D基因突变与缺血性脑卒中的研究

目的为探索浙江南部地区人群5-脂氧合酶激活蛋白(ALOX5AP)基因中SG13S89、SG13S114和磷酸二酯酶4D(PDE4D)基因中单核苷酸多态性83与缺血性脑卒中的关系。方法选择脑梗死患者394例为脑梗死组,另选无脑梗死382例为对照组。采用PCR和基质辅助激光解析/电离飞行时间质谱法,分析ALOX5AP基因中的SG13S89(rs4769874)、SG13S114(rs10507391)和PDE4D基因中单核苷酸多态性83(rs966221)的多态性。结果与对照组比较,脑梗死组SG13S89基因AG型、A等位基因频率明显升高(4.1%vs 1.3%,P<0.05;2.0%vs0.7%,P<0.05);。多因素logistic回归分析显示,调整高血压、糖尿病和年龄后,SG13S89的AG基因型相对于GG基因型有较高的脑卒中风险(OR=4.24,95%CI:1.17～15.32,P=0.027)。SG13S89等位基因分布与大动脉粥样硬化型和小动脉闭塞型脑梗死差异无统计学意义(P>0.05)。SG13S89的AG基因型与女性人群发生脑卒中相关(P=0.022),但A等位基因在女性脑卒中人群中差异无统计学意义(P>0.05)。结论 rs4769874AG基因型和A等位基因频率可增高缺血性脑卒中风险,可能是该基因与血管炎性反应和通透性增加导致脑梗死的机制相关。但未发现PDE4D基因单核苷酸多态性83突变与脑卒中相关。     

5-脂氧合酶激活蛋白（ALOX5AP）基因单倍体型与心肌梗死易感性相关：人类基因组流行病学研究的荟萃分析

目的既往研究提示ALOX5AP基因变异与心肌梗死（Myocardial infarction,MI）相关,但这些研究大多样本较小,结论亦不一致。本文拟系统评价ALOX5AP基因变异与MI易感性的关系。对象与方法系统检索PubMed（1967．1—2009．5）、Embase（1967．1-2009．5）数据库及维普（1989．2009）、CNKI（1979—2009）中文期刊数据库,并通过阅读相关综述及文章的参考文献进一步获取信息。对目前已发表的评估ALOX5AP基因变异与MI关系的候选基因关联研究进行荟萃分析。应用固定效应模型（Fixed—effect models）计算比值比（Oddsratio,OR）及其95％可信限（CI）,用以描述ALOX5AP基因变异与MI的关系。结果共有5项探讨ALOX5AP基因HapA单倍体型（SG13S25G—SG13S114T．SG13S89G—SG13S32A）与MI关系的研究（合计MI病例2778人,对照2484人）及4项评估ALOX5AP基因HapB单倍体型（SG13S377A—SG13S114A—SG13S41A—SG13S35G）与MI关系的研究（合计MI病例1999人,对照1860人）纳入荟萃分析。5项关于HapA单倍体型的研究间无明显异质性（P=0．111,I^2=46．8％）。与非携带者相比,ALOX5AP基因HapA单倍体型携带者使MI的易感性增加24％（OR：1．24,95％可信限1．06—1．45,P=0．006）。4项关于HapB的研究亦无明显异质性（P=0．148,I^2=43．9％）;与非携带者相比,ALOX5AP基因HapB单倍体型携带者使MI的易感性增加31％（OR：1．31,95％可信限1．01—1．70,P=0．04）。结论本研究提示ALOX5AP基因HapA、HapB单倍体型与MI的易感性增加有关。     

不稳定型心绞痛患者MCP-1-2518G/A多态性和血清单核细胞趋化蛋白水平的相关性

目的 探索中国苏南地区汉族人群的单核细胞趋化蛋白-1( MCP-1 )-2518G/A多态性、血清MCP-1水平和不稳定型心绞痛(UAP)三者之间的相关性.方法 采用PCR-RFLP方法检测203例UAP患者(UAP组)和192例经冠脉造影检查证实无冠脉病变者(对照组)的MCP-1 -2518G/A多态性；采用ELISA法随机检测UAP组72例、对照组73例的血清MCP-1水平.结果 与对照组比较,MCP-1-2518G/A位点基因型频率较高(P=0.04),G等位基因频率较低(P=0.044)；经校正年龄、性别、高血压、糖尿病、吸烟及血脂异常等冠心病传统危险因素后,MCP-1-2518 G/A多态性不增加UAP的易感性(P＞0.05).UAP组与对照组组内任何基因型间血清MCP-1水平无显著差异(P＞0.05)；UAP组血清MCP-1水平[( 286.23±284.20) pg/ml]显著高于对照组[(172.61±178.70) pg/ml,P =0.005].多元线性回归分析显示血清MCP-1与高血压、糖尿病、吸烟、性别相关.多变量Logistic回归分析揭示≥75%分位数的血清MCP-1水平与UAP的发病风险相关[OR(95%CI):2.904( 1.058 ～7.970),P=0.039].结论中国苏南地区汉族人群MCP-1 -2518G/A多态性与UAP易感性无明显关联,UAP患者和非冠心病者该基因位点多态性对血清MCP-1水平无影响,UAP患者血清MCP-1水平显著升高且≥75%分位数的MCP-1血清水平可能是UAP的独立危险因素.     

ALOX5AP与卒中

ALOX5AP位于染色体13q12-13,编码5-脂氧合酶激活蛋白(FLAP)。FLAP在调节白细胞三烯的形成中起关键作用。研究表明,携带此基因的人群患卒中的风险增高2倍。因此,ALOX5AP在卒中的发病机制中起着重要作用。     

不稳定心绞痛男性患者血浆纤溶酶原激活物抑制物-1抗原水平及启动子基因多态性研究

目的　探讨纤溶酶原激活物抑制物 1(PAI 1)血浆抗原水平及基因启动子 - 6 75 4G/ 5G、- 84 4G→A多态性与男性不稳定心绞痛 (UAP)的关系。方法选择男性UAP患者 74例 (UAP组 ) ,冠脉造影正常者 6 8例 (对照组 ) ,以ELISA法测定PAI 1血浆抗原水平 ,PCR扩增特定DNA片段 ,琼脂糖电泳确定 - 6 75 4G/ 5G多态性位点基因型 ,XhoⅠ酶切及琼脂糖电泳确定 - 84 4G→A多态性位点基因型。结果UAP组血浆PAI 1抗原水平显著高于对照组 (6 7 86± 32 5 9ng/ml比 5 1 35± 17 95ng/ml,P <0 0 1)。血浆PAI 1抗原水平与血糖 (Glu)水平正相关rs=0 2 37(P =0 0 0 4 )。UAP组 4G、4G纯合子及 4G等位基因频率显著高于对照组 ,- 84 4位点三种基因型及A、G等位基因频率在两组间分布无差别。 4G及G等位基因与较高的血浆PAI 1抗原水平有关 ,4G/ 4G及AG/GG基因型者UAP组血浆PAI 1抗原水平显著高于对照组。Logistic回归分析显示血浆PAI 1抗原水平及Glu水平与UAP发生有关。结论　PAI 1基因启动子 - 6 75 4G/ 5G ,- 84 4G→A基因多态性与不稳定心绞痛的发生无关 ,但 4G及G等位基因携带者存在较高的PAI 1抗原水平 ,血浆PAI 1抗原水平及Glu水平是UAP发生的危险因素。     

The association between the gene encoding 5-lipoxygenase activating protein and abdominal aortic aneurysms

BackgroundGenetic variation in the gene ALOX5AP, encoding arachidonate 5-lipoxygenase-activating protein, have been suggested to increase risk for myocardial infarction and stroke. Leukotrienes (LTs) that derive from the 5-lipoxygenase (5-LO) cascade have been implicated in the pathogenesis of abdominal aortic aneurysm (AAA).Methods and resultsThe association of the ALOX5AP haplotypes with AAA was assessed in a large population-based cohort of 613 men aged ≥65 years with screen-detected AAAs and 707 randomly selected age-matched controls without AAA. Taqman assays were used to assess seven previously described single nucleotide polymorphisms (SNPs) of ALOX5AP. Haplotypes A and B were defined by the four SNPs (SG13S25, SG13S114, SG13S89, SG13S32) and (SG13S377, SG13S114, SG13S41, SG13S35), respectively. After adjustment for cardiovascular risk factors, there were no significant differences in the distribution of ALOX5AP haplotypes between cases and controls.ConclusionA genetic predisposition to up-regulation of LT mediators is unlikely to play a dominant role in the pathogenesis of AAA.     

Association between ALOX5AP gene polymorphisms and coronary artery disease in the Han population of North China

Objectives Recent evidence have implicated specific gene polymorphisms of arachidonate 5-lipoxygenase-activating protein(ALOX5AP),and 2 at-risk haplotypes (HapA,HapB ) in myocardial infarction(MI) and stroke, whereas other studies have been conflicting and to date,no data concerning coronary artery disease(CAD) are available in the Han population of North China.The aim of the present study was to investigate the possible associations between the variants of ALOX5AP gene and susceptibility to CAD in the Han population of North China.Methods We sequenced the promoter,all of the exons,splite site region and 3’untranslated region of ALOX5AP gene,and 7 single nucleotide polymorphisms(SNPs) were found.Three(-1340T/G,+ 8733T/C,+20616G/C) of these polymorphisms were evaluated in 656 patients with angiographically proven CAD and 678 controls with normal coronary angiograms using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay.Allelic,genotypic and haplo-typic association testing were performed using Shesis and Phase version 2.1 software package.Multiple logistic regression was used to control for the presence of vascular risk factors.Results While none of the single nucleotide polymorphism (SNP) was found to be associated with CAD risk individually,there was an association with the 3 SNP haplo-types. We identified a protective haplotype -1340T,+8733C and +20616G(Bonferroni-corrected P=0.000002984,OR = 0.623,95%CI=0.519-0.748) and a risk haplotype -1340G, +8733C and +20616G(Bonferroni-corrected P =0.000018, OR=1.728,95%CI=1.375-2.171).The frequencies of all alleles were in Hardy |= Weinberg equilibrium.Conclusions Our data suggest that unique haplotype combinations in the ALOX5AP gene may play a role in the etiology of CAD.     

支气管哮喘患者白三烯基因多态性与抗白三烯治疗的相关性研究

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.

Abstract：

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.     

Low leukotriene B4 receptor 1 leads to ALOX5 downregulation at diagnosis of chronic myeloid leukemia

ALOX5 is implicated in chronic myeloid leukemia development in mouse leukemic stem cells, but its importance in human chronic myeloid leukemia is unknown. Functional ALOX5 was assessed using an LTB4 ELISA and ALOX5, and LTB4R1 mRNA expression was determined via a TaqMan gene expression assay. LTB4R1 and 5-LOX protein levels were assessed by cell surface flow cytometry analysis. At diagnosis ALOX5 was below normal in both blood and CD34⁺ stem cells in all patients. On treatment initiation, ALOX5 levels increased in all patients except those who were destined to progress subsequently to blast crisis. LTB4 levels were increased despite low ALOX5 expression, suggesting that the arachidonic acid pathway is functioning normally up to the point of LTB4 production. However, the LTB4 receptor (BLT1) protein in newly diagnosed patients was significantly lower than after a period of treatment (P<0.0001). The low level of LTB4R1 at diagnosis explains the downregulation of ALOX5. In the absence of LTB4R1, the arachidonic acid pathway intermediates (5-HEPTE and LTA4) negatively regulate ALOX5. ALOX5 regulation is aberrant in chronic myeloid leukemia patients and may not be important for the development of the disease. Our data suggest caution when extrapolating mouse model data into human chronic myeloid leukemia.     

ALOX5AP expression, but not gene haplotypes, is associated with obesity and insulin resistance

OBJECTIVE: Inflammation in adipose tissue may link obesity to insulin resistance and atherosclerosis. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) gene is involved in the pathogenesis of atherosclerotic cardiovascular disease (CVD). We investigated ALOX5AP expression in adipose tissue, and association of gene polymorphisms with obesity and insulin resistance. DESIGN: For gene expression analysis in adipose tissue, we studied 12 lean and 36 obese women, eight lean and 13 obese men, and nine women before and 2-4 years after gastric banding surgery. For genetic analysis, we studied 231 nonobese and 350 obese men. RESULTS: The ALOX5AP protein, 5-lipoxygenase activating protein (FLAP), as well as 5-lipoxygenase (5LO) itself, were detected in adipocytes. The mRNA expression of ALOX5AP in subcutaneous adipose tissue was increased in obesity and normalized following weight reduction. High adipose tissue mRNA expression of ALOX5AP is associated with insulin resistance as measured by homeostasis model assessment (HOMA(IR)). ALOX5AP haplotypes that associate with CVD are not associated with obesity or insulin resistance. CONCLUSION: ALOX5AP is present in adipose tissue, where its expression is associated with body weight and HOMA(IR), and may provide a link between adipose tissue, inflammation and insulin resistance. Investigated ALOX5AP haplotypes are not major primary risk factors for obesity and insulin resistance.     

ALOX5AP基因多态2354T/A和MTHFR基因多态677C/T的协同作用显著增加脑梗塞的易患性

目的研究MTHFR多态性和编码5-脂氧合酶激活蛋白的基因ALOX5AP多态性，尤其是基因之间的相互作用，是否与脑卒中的易患性相关。方法采用PCR．RFLP方法，对来自7个临床中心的1823名对照和1832名脑卒中患者检测了基因ALOX5AP和MTHFR的3个多态性，基因分型结果经测序进一步确证。多元logistic回归方法校正了传统危险因素后分析基因多态性与脑卒中的独立相关性。检测7个与脑卒中不相关的微卫星多态标记在病例一对照人群的频率分布以评估人群层化程度。结果MTHFR677TT基因型与男性脑梗塞的发病风险呈弱相关（OR，1．45；95％CI：1．04-2．02；P=0．020），ALOX5AP2354AA基因型也增加男性脑梗塞1．55倍的发病风险（95％CI：1．03．2．35；PP=0．038）。当个体同时携带MTHFR677TT和ALOX5AP2354AA基因型时，男性脑梗塞的相对患病风险率显著增加至3．58倍（（95％CI：1．72-7．43；P=0．001）。微卫星多态性标记的各主要等位基因片段的频率在病例和对照组无显著性差异。结论MTHFR677TT基因型和ALOX5AP2354AA基因型的协同作用与增加的男性脑梗塞患病风险呈显著相关。对于多因素复杂性疾病，综合分析弱效基因的相互作用有助于了解个体易患脑卒中的遗传背景。