中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2013年
28期
2195-2199
,共5页
高静%丛洪良%毛用敏%刘祎%张楠%陈倩%刘婷%崔让庄
高靜%叢洪良%毛用敏%劉祎%張楠%陳倩%劉婷%崔讓莊
고정%총홍량%모용민%류의%장남%진천%류정%최양장
冠状动脉疾病%胆固醇酯转运蛋白质类%阿托伐他汀%多态性%药物基因组学
冠狀動脈疾病%膽固醇酯轉運蛋白質類%阿託伐他汀%多態性%藥物基因組學
관상동맥질병%담고순지전운단백질류%아탁벌타정%다태성%약물기인조학
Coronary disease%Cholesteryl ester transfer protein%Atorvastatin%Polymorphism%Pharmacogenomics
目的 分析天津地区汉族冠心病患者胆固醇酯转运蛋白(CETP)-629C/A基因多态性,从药物基因组学角度探讨遗传因素对阿托伐他汀钙调脂疗效及患者长期临床预后的影响,为临床个体化治疗提供理论依据.方法 研究对象来自2010年10月至2011年7月天津市胸科医院心内科住院经冠状动脉造影检查证实的冠心病患者共332例,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CETP-629C/A基因型,ELISA方法测定血清CETP含量.所有患者接受阿托伐他汀钙20 mg调脂治疗1年后复查血脂,随访12～ 23个月,记录主要不良心血管事件(MACE)[包括死亡、非致死性心肌梗死(MI)、再次血运重建和卒中].采用Kaplan-Meier生存曲线Log-rank检验分析不同基因型对生存率的影响.结果 (1)A突变基因频率为0.476,C等位基因频率为0.524;CC、CA、AA基因型比较,血清高密度脂蛋白胆固醇(HDL-C)水平呈升高趋势,血清CETP水平呈降低趋势,差异均无统计学意义(分别F=0.893,P=0.411和F=1.279,P=0.282)；血清HDL-C水平与CETP浓度呈负向变化趋势,其相关性差异无统计学意义(r=-0.151,P=0.081).(2)阿托伐他汀钙20 mg调脂治疗1年后,CC基因型携带者低密度脂蛋白胆固醇(LDL-C)水平下降最多为43.5％,CA基因型次之为25.5％,AA基因型下降最少为11.7％,差异有统计学意义(P=0.001)；血清脂蛋白a[LP(a)]水平变化在不同基因型3组间差异有统计学意义(P =0.004),CC基因型下降最明显为44.2％；3种基因型患者HDL-C水平的变化虽然表现出梯度变化趋势,但差异无统计学意义(P=0.412),CC基因型HDL-C水平升高最明显为9.2％,CA基因型为6.8％,AA基因型为5.5％；对胆固醇、甘油三酯、极低密度脂蛋白胆固醇、载脂蛋白AI、载脂蛋白B的调节效果没有受到CETP多态性的影响.(3)随访(18.7±6.0)个月,发生MACE 26例(7.83％),其中死亡3例(0.90％),MI7例(2.11％),再次血运重建13例(3.92％),卒中3例(0.90％).3种基因型无MACE生存率分别为CC型96.2％,CA型92.1％,AA型87.3％,差异无统计学意义(Log-rank P =0.444).结论 -629AA基因型患者具有较高基线HDL-C水平和较低CETP浓度,但-629CC基因型携带者有更好的他汀类调脂效果,LDL-C和LP(a)水平下降更明显,3种基因型患者长期临床预后无显著差异.
目的 分析天津地區漢族冠心病患者膽固醇酯轉運蛋白(CETP)-629C/A基因多態性,從藥物基因組學角度探討遺傳因素對阿託伐他汀鈣調脂療效及患者長期臨床預後的影響,為臨床箇體化治療提供理論依據.方法 研究對象來自2010年10月至2011年7月天津市胸科醫院心內科住院經冠狀動脈造影檢查證實的冠心病患者共332例,採用聚閤酶鏈反應-限製性片段長度多態性(PCR-RFLP)方法檢測CETP-629C/A基因型,ELISA方法測定血清CETP含量.所有患者接受阿託伐他汀鈣20 mg調脂治療1年後複查血脂,隨訪12～ 23箇月,記錄主要不良心血管事件(MACE)[包括死亡、非緻死性心肌梗死(MI)、再次血運重建和卒中].採用Kaplan-Meier生存麯線Log-rank檢驗分析不同基因型對生存率的影響.結果 (1)A突變基因頻率為0.476,C等位基因頻率為0.524;CC、CA、AA基因型比較,血清高密度脂蛋白膽固醇(HDL-C)水平呈升高趨勢,血清CETP水平呈降低趨勢,差異均無統計學意義(分彆F=0.893,P=0.411和F=1.279,P=0.282)；血清HDL-C水平與CETP濃度呈負嚮變化趨勢,其相關性差異無統計學意義(r=-0.151,P=0.081).(2)阿託伐他汀鈣20 mg調脂治療1年後,CC基因型攜帶者低密度脂蛋白膽固醇(LDL-C)水平下降最多為43.5％,CA基因型次之為25.5％,AA基因型下降最少為11.7％,差異有統計學意義(P=0.001)；血清脂蛋白a[LP(a)]水平變化在不同基因型3組間差異有統計學意義(P =0.004),CC基因型下降最明顯為44.2％；3種基因型患者HDL-C水平的變化雖然錶現齣梯度變化趨勢,但差異無統計學意義(P=0.412),CC基因型HDL-C水平升高最明顯為9.2％,CA基因型為6.8％,AA基因型為5.5％；對膽固醇、甘油三酯、極低密度脂蛋白膽固醇、載脂蛋白AI、載脂蛋白B的調節效果沒有受到CETP多態性的影響.(3)隨訪(18.7±6.0)箇月,髮生MACE 26例(7.83％),其中死亡3例(0.90％),MI7例(2.11％),再次血運重建13例(3.92％),卒中3例(0.90％).3種基因型無MACE生存率分彆為CC型96.2％,CA型92.1％,AA型87.3％,差異無統計學意義(Log-rank P =0.444).結論 -629AA基因型患者具有較高基線HDL-C水平和較低CETP濃度,但-629CC基因型攜帶者有更好的他汀類調脂效果,LDL-C和LP(a)水平下降更明顯,3種基因型患者長期臨床預後無顯著差異.
목적 분석천진지구한족관심병환자담고순지전운단백(CETP)-629C/A기인다태성,종약물기인조학각도탐토유전인소대아탁벌타정개조지료효급환자장기림상예후적영향,위림상개체화치료제공이론의거.방법 연구대상래자2010년10월지2011년7월천진시흉과의원심내과주원경관상동맥조영검사증실적관심병환자공332례,채용취합매련반응-한제성편단장도다태성(PCR-RFLP)방법검측CETP-629C/A기인형,ELISA방법측정혈청CETP함량.소유환자접수아탁벌타정개20 mg조지치료1년후복사혈지,수방12～ 23개월,기록주요불양심혈관사건(MACE)[포괄사망、비치사성심기경사(MI)、재차혈운중건화졸중].채용Kaplan-Meier생존곡선Log-rank검험분석불동기인형대생존솔적영향.결과 (1)A돌변기인빈솔위0.476,C등위기인빈솔위0.524;CC、CA、AA기인형비교,혈청고밀도지단백담고순(HDL-C)수평정승고추세,혈청CETP수평정강저추세,차이균무통계학의의(분별F=0.893,P=0.411화F=1.279,P=0.282)；혈청HDL-C수평여CETP농도정부향변화추세,기상관성차이무통계학의의(r=-0.151,P=0.081).(2)아탁벌타정개20 mg조지치료1년후,CC기인형휴대자저밀도지단백담고순(LDL-C)수평하강최다위43.5％,CA기인형차지위25.5％,AA기인형하강최소위11.7％,차이유통계학의의(P=0.001)；혈청지단백a[LP(a)]수평변화재불동기인형3조간차이유통계학의의(P =0.004),CC기인형하강최명현위44.2％；3충기인형환자HDL-C수평적변화수연표현출제도변화추세,단차이무통계학의의(P=0.412),CC기인형HDL-C수평승고최명현위9.2％,CA기인형위6.8％,AA기인형위5.5％；대담고순、감유삼지、겁저밀도지단백담고순、재지단백AI、재지단백B적조절효과몰유수도CETP다태성적영향.(3)수방(18.7±6.0)개월,발생MACE 26례(7.83％),기중사망3례(0.90％),MI7례(2.11％),재차혈운중건13례(3.92％),졸중3례(0.90％).3충기인형무MACE생존솔분별위CC형96.2％,CA형92.1％,AA형87.3％,차이무통계학의의(Log-rank P =0.444).결론 -629AA기인형환자구유교고기선HDL-C수평화교저CETP농도,단-629CC기인형휴대자유경호적타정류조지효과,LDL-C화LP(a)수평하강경명현,3충기인형환자장기림상예후무현저차이.
Objective To explore the polymorphism of cholesteryl ester transfer protein (CETP) gene-629C/A among the coronary heart disease (CHD) Han population of Tianjin area and evaluate the influences of genetic factors on atorvastatin therapeutic effects and clinical outcomes in pharmacogenomics and provide theoretical rationales for individualized treatment.Methods A total of 332 angiographically confirmed CHD patients at Tianjin Chest Hospital were recruited from October 2010 to July 2011.The CETP gene promoter polymorphism at position-629 was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP).The serum level of CETP was determined by enzyme-linked immunosorbent assay (ELISA).Lipid levels were determined at baseline and 12 months post-treatment with 20 mg/d atorvastatin in all patients.Clinical follow-up were performed for more than 1 year (range,12-23 months).And major adverse cardiac events (MACE,including death,non-fatal infarction,revascularization and stroke) were analyzed.The Kaplan-Meier Log-rank test was used to compare MACE-free survival between different genotypes.Results (1) The frequencies of variant-692A allele was 0.476,AA genotype showed reduced CETP levels and higher HDL-C levels compared with CC and CA genotypes.But it did not reach statistical significance (F =0.893,P =0.411 and F =1.279,P =0.282 respectively).Although a negative trend correlation existed between serum levels of HDL-C and CETP,it did not reach statistical significance (r =-0.151,P =0.081).(2) After 12-month therapy of atorvastatin,CC genotype was shown to be associated with higher LDL-C,LP (a) reduction and HDL-C elevation in response to atorvastatin compared with CA and AA genotype.LDL-C levels decreased 43.5％ in CC homozygotes,25.5％ in CA heterozygotes and 11.7％ in AA homozygotes (P =0.001).HDL-C levels increased 9.2％ in CC homozygotes,6.8％ in CA heterozygotes and 5.5％ in AA homozygotes.However the changes of HDL-C levels in three genotypes showed no significant difference (P =0.412).(3)There was a 7.83％ incidence of MACE after a mean follow-up of (18.66 ± 5.99) months.The outcomes were death (n =3,0.90％),nonfatal infarction (n =7,2.11％),revascularization (n =13,3.92％) and stroke (n =3,0.90％).The cumulative MACE free survival rates were 96.2％,92.1％ and 87.3％ in CC,CA and AA genotypes respectively (Log-rank P =0.444).Conclusion Variant AA genotype shows a higher level of HDL-C s and a lowered level of CETP.However CC genotype offers a better benefit of statin therapy associated with lowered levels of LDL-C and LP(a).And the long-term clinical prognosis is not affected among three genotypes.
