环氧化酶-2基因-765G〉C和前列环素合酶基因C1117A多态性与新疆维吾尔族人群心肌梗死的相关性研究

Study on the association of cyclooxygenas-2 -765G 〉 C and prostacyclin synthase C1117A polymorphisms and the risk of myocardial infarction in Uigur population of Xinjiang,China

目的 探讨环氧化酶-2（COX-2）基因-765G〉C和前列环素合酶（PGIS）基因C1117A多态性与新疆维吾尔族人群心肌梗死的相关性。方法 采用聚合酶链反应-限制性片段长度多态性方法，对新疆维吾尔族178例心肌梗死患者和175名健康体检者COX-2基因-765G〉C和PGIS基因C1117A多态性进行检测，同时进行血清6-酮-列环素F1。水平及其他生化指标测定。结果 （1）PGIS基因C1117A不同基因型在心肌梗死组和健康对照组中频率分别为：CC型75．84％和64．57％，CA型17．42％和28．29％，AA型6．74％和9．14％，两组基因型和等位基因频率差异具有统计学意义（P〈0．05）；（2）COX-2基因-765GG基因型在心肌梗死组为78．65％，明显高于对照组（55．43％），差异具有统计学意义（P〈0．01），但-765GC和-765CC基因型在心肌梗死组分布频率（19．66％和1．69％）明显低于健康对照组（34．86％和9．71％），差异具有统计学意义（P〈0．05或P〈0．01），且等位基因频率差异亦有统计学意义（P〈0．01）；（3）联合基因分析显示，心肌梗死组PGIS基因1117CC基因型＋COX-2基因-765GG基因型频率显著高于对照组（P〈0．01），具有该联合基因型者发生心肌梗死的风险（OR=3．87）明显高于单独具有PGIS基因1117CC基因型（OR=1．72）或COX-2基因-765GG基因型（OR=2．94）者；（4）心肌梗死组6-酮-前列环素F1。水平较对照组降低，差异具有统计学意义（P〈0．05）；在PGIS基因C1117A不同基因型之间及COX-2基因-765G〉C不同基因型之间，6-酮-前列环素F1。水平的差异无统计学意义（P〉0．05）；但具有COX-2基因-765GG＋PGIS基因1117CC联合基因型者6-酮-前列环素F1。水平明显降低于其他基因型，差异具有统计学意义（P〈0．05）。结论PGIS基因CC基因型和C等位基因及COX-2基因-765GG基因型和G等位基因与新疆维吾尔族人群心肌梗死的发生具有相关性；携带COX-2基因-765GG＋PGIS基因CC联合基因型者发生心肌梗死的风险显著增加，可能和该联合基因型导致的血清前列环素水平降低有关；COX-2基因-765CC基因型和C等位基因可能是新疆维吾尔族人群心肌梗死发生的保护因子。

Objective The purpose of this study was to investigate the association of genetic polymorphism of cyclooxygenase-2 and prostacyclin synthase with myocardial infarction （MI） in Uigur population in Xinjiang. Methods 178 patients with MI and 175 healthy control subjects were detected on the genetic polymorphism of cyclooxygenase-2 and prostacyclin synthase by polymerase chain reaction-based restriction fragment length polymorphism. Other serum 6-keto-PGF1a concentration and biochemical indicators were detected in all the subjects. Results （ 1 ） The genotype distributions of the control group and MI group were in the Hardy-Weinberg equilibrium. The frequencies of CC, CA and AA genotype of prostacyclin synthase were 75.84% ,17.42% and 6.74% in MI group while they were 64.57% ,28.29% and 9.14 % in controls respectively. There was significant difference in frequencies of CC genotype and C allele as well as CA and AA genotypes between controls and MI cases. （2）The frequencies of -765GG, -765GC and -765CC genotype of cyclooxygenase-2 were 78.65 %, 19.66 % and 1.69 % in MI group while they were 55.43%, 34.86% and 9.71% in controls respectively. There was significant difference in frequencies of three genotypes and alleles between the two groups （P〈 0.05 or P〈 0.01 ）. （3） In combined genotype analysis, the genotype of PGIS CC ＋ COX-2 -765GG was significantly higher in patients with MI than in control subjects （P 〈 0.05）. The odds ratio estimated through combined analysis of the PGIS CC and COX-2 -765GG genotypes（ OR = 3.87） markedly increased when compared with that estimated separately from the PGIS CC （ OR = 1.72） or COX-2 -765GG （ OR = 2.94） genotype. （4） There was a significant difference in serum 6-keto-PGF2a level between MI group and control group （P〈 0.05） ,but there were no differences found in every genotype of PGIS and COX-2 gene （ P 〉0.05）. In the cases with both COX-2 -765GG and PGIS CC genotypes, the serum 6-keto-PGF1a levels was lower than that of others （P 〈 0.05）. Conclusion The CC genotype and C allele of prostacyclin synthase, -765GG genotype and G allele of COX-2 might serve as risk factors of MI of Uigur population in Xinjiang. Populations with both COX-2 -765GG and PGIS CC genotypes were more at risk with MI than others which might be resulted from the decreased serum 6-keto-PGF1a concentration. The -765CC genotype and C allele of COX-2 gene might have protective functions on MI among Uigur population in Xinjiang.