纤维蛋白原β链启动因子基因多态性与颈动脉粥样硬化斑块稳定性的关联性研究

Correlation between polymorphisms of fibrinogenβ-chain promoter gene and the stability of carotid atherosclerotic plaques

目的:探究纤维蛋白原β链启动因子基因多态性与颈动脉粥样硬化斑块稳定性的关联性。方法:选取2020年1月至2021年12月于梧州市红十字会医院住院的脑梗死患者256例为研究组,其中颈动脉粥样硬化斑块组(斑块组)194例,无斑块组62例,根据斑块是否稳定,将斑块组分为稳定组和不稳定组,分别有91例和103例,并纳入同期200例体检健康人群作为对照组。采用聚合酶链-限制性片段长度多态性技术检测纤维蛋白原β链启动因子基因rs4220、rs6050、rs1800787、rs1800790及rs1800791位点基因型。采用χ2检验比较研究组与对照组、斑块组与无斑块组、稳定组和不稳定组组间基因分布差异;采用二元Logistic回归模型筛选脑梗死患者颈动脉不稳定斑块发生的危险因素。结果:研究组和对照组纤维蛋白原β链启动因子基因rs4220、rs6050、rs1800790、rs1800791位点基因型及等位基因,rs1800787位点等位基因分布比较,差异具有统计学意义(P<0.05),其中,与对照组比较,研究组rs4220位点G等位基因(75.59% vs 51.50%)、rs6050位点A等位基因(69.53% vs 59.50%)、rs1800787位点C等位基因(81.25% vs 74.50%)、rs1800790位点G等位基因(74.80% vs 58.25%)、rs1800791位点A等位基因(10.16% vs 2.50%)频率高,差异具有统计学意义(χ2=57.280,P<0.001;χ2=9.950,P=0.002;χ2=6.020,P=0.014;χ2=28.073,P<0.001;χ2=20.775,P<0.001);斑块组和无斑块组纤维蛋白原β链启动因子基因rs4220和rs1800790位点基因型及等位基因、rs1800791位点等位基因分布比较,差异具有统计学意义(P<0.05),其中,与无斑块组比较,斑块组rs4220位点G等位基因(79.38% vs 63.71%)、rs1800790位点G等位基因(77.58% vs 66.13%)、rs1800791位点A等位基因(11.86% vs 4.84%)频率高,差异具有统计学意义(χ2=12.507,P<0.001;χ2=6.535,P=0.011;χ2=5.071,P=0.024);稳定组和不稳定组rs4220位点等位基因、rs1800790和rs1800791位点基因型及等位基因分布比较,差异具有统计学意义(P<0.05),其中,与稳定组比较,不稳定组rs4220位点G等位基因(83.50% vs 74.73%)、rs1800790位点G等位基因(83.01% vs 71.43%)、rs1800791位点A等位基因(15.53% vs 7.69%)频率高,差异具有统计学意义(χ2=4.541,P=0.033;χ2=7.451,P=0.006;χ2=5.686,P=0.017)。Logistic回归分析显示,糖尿病、rs4220、rs1800790位点G等位基因是脑梗死患者颈动脉不稳定斑块发生的独立危险因素(OR=1.696、1.530、1.456,95%CI:1.104~2.604、1.066~2.194、1.004~2.114,P=0.016、0.021、0.048)。结论:纤维蛋白原β链启动因子rs4220、rs1800790位点G等位基因可能增加脑梗死患者颈动脉斑块的不稳定性,加重病情。

Objective To explore the correlation between polymorphisms of fibrinogenβ-chain promoter gene and the stability of carotid atherosclerotic plaques.Methods A total of 256 patients with cerebral infarction in Wuzhou Red Cross Hospital were enrolled as the study group between January 2020 and December 2021,including 194 cases in the carotid atherosclerotic plaque group the(plaque group)and 62 cases in the non-plaque group.According to plaque stability,patients in the plaque group were divided into the stable subgroup(91 cases)and the unstable subgroup group(103 cases).A total of 200 healthy controls during the same period were enrolled as the control group.The genotypes of fibrinogenβ-chain promoter gene at rs4220,rs6050,rs1800787,rs1800790,and rs1800791 loci were detected by polymerase chain reaction-restriction fragment length polymorphism.Theχ2 test was used to compare the difference in gene distribution between the study and the control group,as well as the stable and the unstable subgroup.The binary Logistic regression model was used to screen for risk factors of carotid unstable plaques in patients with cerebral infarction.Results The differences in genotypes and alleles of fibrinogenβ-chain promoter gene at rs4220,rs6050,rs1800790 and rs1800791 loci,and alleles at rs1800787 locus between the study group and the control group were statistically significant(P<0.05).The frequencies of G allele at rs4220 locus,A allele at rs6050 locus,C allele at rs1800787 locus,G allele at rs1800790 locus,and A allele at rs1800791 locus in the study group were higher than those in the control group(P<0.05).The differences in genotypes and alleles of fibrinogenβ-chain promoter gene at rs4220 and rs1800790 loci,and alleles at rs1800791 locus between the plaque group and the non-plaque group were statistically significant(P<0.05).The frequencies of G allele at rs4220 and rs1800790 loci,and A allele at rs1800791 locus in the plaque group were higher than those in the non-plaque group(P<0.05).The differences in alleles at rs4220 locus,genotypes and alleles at rs1800790 and rs1800791 loci between the stable subgroup and the unstable subgroup were statistically significant(P<0.05).The frequencies of G allele at rs4220 and rs1800790 loci,and A allele at rs1800791 locus in the unstable subgroup were higher than those in the stable subgroup(P<0.05).Diabetes mellitus,and G allele at rs4220 and rs1800790 loci were independent risk factors of unstable carotid plaques in patients with cerebral infarction(P<0.05).Conclusion G allele of fibrinogenβ-chain promoter at rs4220 and rs1800790 loci may increase the instability of carotid plaques and aggravate conditions of patients with cerebral infarction.