CAJ | 학술논문

目的研究ADP受体P2Y1基因多态性与阿司匹林抵抗(aspirin resistance AR)是否存在相关性.方法选取2010年10月至2012年3月上海交通大学附属第六人民医院急诊科急诊内科和心内科病房住院患者中40岁以上冠心病、高血压、脑梗死后合并或不合并2型糖尿病患者330例.入院后,进行详细病史采集、查体、及测定相关血液指标.服用阿司匹林(100 mg/d)至少7d后次日晨,抽取肘静脉血2管,光学法分别测定花生四烯酸(arachidonic acid,AA)及二磷酸腺苷(adenosine diphosphate,ADP)诱导的血小板聚集率,根据血小板聚集率,确定患者为AR或阿司匹林敏感(aspirin sensitive,AS).另一管置-80℃冰箱待集中后通过PCR扩增直接测序法检测P2Y1基因893及1622位点多态性.结果 AR者95例,发生率为28.79％；AS者235例,发生率为71.21％；基因测序结果相关性分析发现P2Y1基因的893C＞T变异与AR发生率增加有关OR=3.16 (95％CI1.36～7.16).与AS组临床资料相比AR组在以下3个方面差异具有统计学意义(P ＜0.05):AR组年龄大、糖尿病发生率高、HDL水平低,进一步使用从包括年龄、2型糖尿病、高血压等在内的各种可能的危险因素中通过Logistic回归分析筛选发现,2型糖尿病、高血压病和低HDL水平是发生AR的独立危险因素.结论 P2Y1基因的893C＞T变异与AR相关.年龄大,合并2型糖尿病,血HDL水平低者更易发生AR；合并2型糖尿病或高血压病,低HDL水平是发生AR的独立危险因素.
목적 연구ADP수체P2Y1기인다태성여아사필림저항(aspirin resistance AR)시부존재상관성.방법 선취2010년10월지2012년3월상해교통대학부속제륙인민의원급진과급진내과화심내과병방주원환자중40세이상관심병、고혈압、뇌경사후합병혹불합병2형당뇨병환자330례.입원후,진행상세병사채집、사체、급측정상관혈액지표.복용아사필림(100 mg/d)지소7d후차일신,추취주정맥혈2관,광학법분별측정화생사희산(arachidonic acid,AA)급이린산선감(adenosine diphosphate,ADP)유도적혈소판취집솔,근거혈소판취집솔,학정환자위AR혹아사필림민감(aspirin sensitive,AS).령일관치-80℃빙상대집중후통과PCR확증직접측서법검측P2Y1기인893급1622위점다태성.결과 AR자95례,발생솔위28.79％；AS자235례,발생솔위71.21％；기인측서결과상관성분석발현P2Y1기인적893C＞T변이여AR발생솔증가유관OR=3.16 (95％CI1.36～7.16).여AS조림상자료상비AR조재이하3개방면차이구유통계학의의(P ＜0.05):AR조년령대、당뇨병발생솔고、HDL수평저,진일보사용종포괄년령、2형당뇨병、고혈압등재내적각충가능적위험인소중통과Logistic회귀분석사선발현,2형당뇨병、고혈압병화저HDL수평시발생AR적독립위험인소.결론 P2Y1기인적893C＞T변이여AR상관.년령대,합병2형당뇨병,혈HDL수평저자경역발생AR；합병2형당뇨병혹고혈압병,저HDL수평시발생AR적독립위험인소.
Objective To investigates a group of 2 candidate single nucleotide polymorphisms in P2Y1 gene in the blood platelet aggregation pathway associated with aspirin resistance (AR).Methods A total of 330 patients in the Emergency wards and Cardiovascular Department of Shanghai Sixth People' s Hospital were enrolled from October 2010 to March 2012.All subjects were examined including blood TC、TG、HDL-C、LDL-C,blood routine,fasting blood glucose (FBG).Following a course of aspirin treatment for at least 7 days,platelet aggregation stimulated by arachidonic acid (AA) and adenosine diphosphate (ADP) was observed,and P2Y1 gene polymorphisms were analyzed by polymerase chain reaction and DNA sequencing assay.Results Of 330 patients,95 (28.79％) had AR,and 235 (71.21％) were sensitive to aspirin.Type 2 diabetes (OR =2.773),hypertension (OR =3.992),and low level of HDL (OR =6.087) were independent risk factors for the development of AR,This SNP comprise a T for C base substitution at position 893 of the P2Y1 gene,and associated with increase in aspirin resistance (OR 3.16、95％ CI 1.36-7.16、P =0.04).Conclusions The type Ⅱ diabetescidence,hypertension and low level of HDL were independent risk factors for the development of AR.There is correlation between mutation of P2Y1 gene (893C ＞ T) and aspirin resistance.