血浆内皮素-1基因多态性与冠状动脉痉挛的相关性研究

摘要

目的:探讨国人冠状动脉(冠脉)痉挛患者血浆内皮素-1基因多态性分布频率及其与冠脉痉挛之间的关系.方法:分别对100例冠状动脉痉挛患者(冠脉痉挛组)和120例健康对照人群(健康人群组)进行血浆内皮素-1的DNA测序,比较其外显子-1+138位点(rs10478694)、内含子-4第8002位点(rs2071942)及外显子-5第5665位点(rs5370)的基因多态性分布频率.结果:冠脉痉挛组比健康人群组的外显子-1+138位点4腺嘌呤(A)/4A野生型(2.5% vs 8.0%)及4A/3A杂合型(20.8% vs 30.0%)的发生频率、内含子-4第8002位点鸟嘌呤(G)/A杂合型(33.4% vs 41.0%)及A/A突变型(3.3% vs 12.0%)的发生频率、外显子-5第5665位点G/胸腺嘧啶(T)杂合型(29.2% vs 46.0%)及T/T突变型(5.8% vs 11.0%)发生频率均降低,差异有统计学意义(P＜0.05).冠脉痉挛组比健康人群组的外显子-1+138位点3A/3A突变型(76.7% vs 62.0%)的发生频率、内含子-4第8002位点G/G野生型发生频率(63.3% vs 47.0%)、外显子-5第5665位点G/G野生型的发生频率(65.0% vs 43.0%)均升高,差异均有统计学意义(P＜0.05).冠脉痉挛组比健康人群组3A-G-G单模样本的分布频率降低(0.47 vs 0.65,OR=0.475),而4A-A-T单模样本分布频率升高(0.05 vs 0.01,OR=4.158),差异均有统计学意义(P＜0.05).结论:血浆内皮素-1外显子-1+138位点、内含子-4第8002位点及外显子-5第5665位点基因多态性可能与冠状动脉痉挛的发生密切相关.%Objective:To investigate the plasma endothelin-1 (ET-1)gene polymorphisms in patients with coronary artery spasm.Methods:Our work included two groups, Coronary artery spasm group,n= 100 and Healthy control group,n= 120. Genome DNA was extracted from peripheral vein blood and the sequencing technique was used to detect the ET-1 polymorphisms on the sites of + 138delA(rs10478694) ,G8002A(rs2071942) and G5665T(rs5370) in all subjects.Results:Tbe frequencies of the ET-1 polymorphisms of +138deLA in exon 1 ,C,8002A in intron 4 and G5665T in exon 5 were significantly lower in Coronary artery spasm group than that in Healthy control group: homozygous 4A/4A(2. 5％ vs. 8. 0％ ) ,homozygous 4A/3A( 20. 8％ vs. 30. 0％ ), homozygous G/A ( 33. 4％ vs. 41.0％ ), homozygous A/A ( 3. 3％ vs. 12. 0％ ), homo zygous G/T(29. 2％ vs. 46. 0％ )and homozygous T/T( 5.8％ vs. 11.0％ ), P＜0. 05 respectively. While the other frequencies of the ET-1 pelymorphisms were higher in Coronary artery spasm group than that in Healthy control group: homozygous 3A/3A (76. 7％ vs. 62. 0％ ), homozygous G/G(63. 3％ vs. 47. 0)and homozygous G/G( 65.0％ vs. 43. 0％ ), P＜0. 05 respectively. The frequency of 3-A-G-G was lower(0. 47 vs. 0. 65, OR =0. 475 ) and 4A-A-T was higher( 0. 05 vs. 0. 01, OR =4. 158 ) in Coronary artery spasm group than that in Healthy control group.Conclusion:The ET-1 gene polymorphisms on the site of +138delA,G8002A and G5665T might be associated in certain patients with coronary artery spasm.