CAJ | 학술논문

目的探讨中国北方汉族人群基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)基因多态性与缺血性脑卒中(ischemic stroke,IS)亚型的相关性.方法应用病例对照研究,选取289例急性缺血性脑卒中患者(发病≤3d)和175名同期健康体检者.卒中组按急性卒中治疗低分子肝素试验病因分型法分为大动脉粥样硬化性(large artery atherosclerotic,LAA)脑卒中185例,小动脉闭塞性(small artery occlusion,SAO)脑卒中104例.选取MMP-3基因rs3025058(-11715A/6A),rs522616(-709A/G)及rs679620(133A/G)3个常见单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用聚合酶链反应限制性片段长度多态性或直接测序法对MMP-3基因3个SNP位点进行基因分型.结果 3个位点存在不完全连锁不平衡,且基因多态性均与LAA型脑卒中相关(P＜0.05).在显性模型中,rs3025058位点5A5A+5A6A基因型携带者患LAA型脑卒中的风险是6A6A基因型携带者的1.72倍(P=0.017,OR=1.72,95％CI:1.10～2.69);rs522616位点GG+ AG基因型携带者患LAA型脑卒中的风险是AA基因型携带者的0.52倍(P=0.005,OR=0.52,95％CI:0.33～0.82)；rs679620位点AA+ GA基因型携带者患LAA型脑卒中的风险是AA基因型携带者的1.55倍(P=0.042,OR=1.55,95％CI:1.01～2.37).但是,3个SNPs基因型和等位基因频率在对照组与SAO型脑卒中之间差异无统计学意义(P＞0.05).另外,LAA组5A-A-A及6A-A-A单倍型高于对照组,差异有统计学意义(P＜0.05),而6A-G-G单倍型显著低于对照组(P＜0.01).结论 MMP-3血清水平在LAA型脑卒中急性期增高明显,SAO型脑卒中次之；中国北方汉族人群MMP-3基因rs3025058,rs522616及rs679620多态性可能与LAA型脑卒中易感性相关.
목적 탐토중국북방한족인군기질금속단백매-3(matrix metalloproteinase-3,MMP-3)기인다태성여결혈성뇌졸중(ischemic stroke,IS)아형적상관성.방법 응용병례대조연구,선취289례급성결혈성뇌졸중환자(발병≤3d)화175명동기건강체검자.졸중조안급성졸중치료저분자간소시험병인분형법분위대동맥죽양경화성(large artery atherosclerotic,LAA)뇌졸중185례,소동맥폐새성(small artery occlusion,SAO)뇌졸중104례.선취MMP-3기인rs3025058(-11715A/6A),rs522616(-709A/G)급rs679620(133A/G)3개상견단핵감산다태성(single nucleotide polymorphisms,SNPs)위점,응용취합매련반응한제성편단장도다태성혹직접측서법대MMP-3기인3개SNP위점진행기인분형.결과 3개위점존재불완전련쇄불평형,차기인다태성균여LAA형뇌졸중상관(P＜0.05).재현성모형중,rs3025058위점5A5A+5A6A기인형휴대자환LAA형뇌졸중적풍험시6A6A기인형휴대자적1.72배(P=0.017,OR=1.72,95％CI:1.10～2.69);rs522616위점GG+ AG기인형휴대자환LAA형뇌졸중적풍험시AA기인형휴대자적0.52배(P=0.005,OR=0.52,95％CI:0.33～0.82)；rs679620위점AA+ GA기인형휴대자환LAA형뇌졸중적풍험시AA기인형휴대자적1.55배(P=0.042,OR=1.55,95％CI:1.01～2.37).단시,3개SNPs기인형화등위기인빈솔재대조조여SAO형뇌졸중지간차이무통계학의의(P＞0.05).령외,LAA조5A-A-A급6A-A-A단배형고우대조조,차이유통계학의의(P＜0.05),이6A-G-G단배형현저저우대조조(P＜0.01).결론 MMP-3혈청수평재LAA형뇌졸중급성기증고명현,SAO형뇌졸중차지；중국북방한족인군MMP-3기인rs3025058,rs522616급rs679620다태성가능여LAA형뇌졸중역감성상관.
Objective To assess the association between matrix metalloproteinase-3 (MMP-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population.Method A total of 289 patients with acute IS (within 3 days after the onset,including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequence-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene.Results An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs,and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model:Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017,OR=1.72,95％CI=1.10-2.69),carriers of G alleles (GG+ AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005,OR=0.52,95％CI=0.33-0.82),whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042,OR =1.55,95％CI=1.01-2.37).However,no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P＞0.05).Furthermore,5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P＜0.05),whilst 6A-G-G haplotype has been the opposite (P＜ 0.01).Conclusion Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes.There may be an association of rs3025058,rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.