| Coronary heart disease is caused by atherosclerosis(accumulation of fatty substances and cholesterol)in the coronary arteries,causing stenosis or occlusion of the coronary lumen(obstruction of blood supply to the heart),resulting in myocardial ischemia or hypoxia or myocardial necrosis.In recent years,according to the different causes of pathological anatomy and pathophysiological changes,as well as the pathogenesis and treatment principles,coronary heart disease(CHD)can be divided into two categories:(1)chronic coronary artery disease(chronic coronary artery disease).CAD)(2)Acute coronary syndrome(ACS).Acute coronary syndrome is a serious subtype of CHD.It is a vascular wall progressive inflammatory disease based on atherosclerosis(AS).Severe inflammatory reaction promotes instability and rupture of AS plaque.This leads to the development of thrombosis in the coronary arteries,which has a high mortality rate worldwide.Studies have shown that the pro-inflammatory heterodimeric complex cytokine IL-23 and interleukin-17(IL-17)which is secreting by Th17 cell and consists of the IL-23/Th17 inflammatory pathway plays a key role in inflammatory diseases including AS.The IL-23 receptor(IL-23R)is an important component of the IL-23 pathway,which may play a role in ACS based on AS.Objective This study was to investigate the association between IL-23R gene rs6682925T/C locus polymorphism and ACS genetic susceptibility,and to analyze the association between IL-23R gene rs6682925T/C locus polymorphism and ACS severity.Provide scientific and reliable basis for the comprehensive prevention and treatment of pathogenesis of ACS.To investigate the effect of IL-23R gene rs6682925T/C polymorphism on serum sIL-23R expression.Methods A case-control study was used.A total of 180 patients were enrolled in the ACS group.The ACS component was divided into two study groups:90 patients with unstable angina(UA)and 90 patients with myocardial infarction(MI).At the same time,the clinical diagnosis results were 90 patients without atherosclerosis.Single nucleotide polymorphisms(SNPs)of the rs6682925T/C locus of IL-23R gene were analyzed by Sanger sequencing.Serum soluble IL-23R(soluble IL-23R,sIL-23R)concentration was detected by ELISA.The association of IL-23R gene rs6682925 C/T polymorphism with susceptibility to ACS was analyzed by unconditional logistic regression.The serum sIL-23R concentration of TT,TC and CC genotypes of IL-23R gene polymorphism rs6682925T/C was compared,and the effect of IL-23R gene rs6682925T/C polymorphism on serum sIL-23R expression was investigated.Results 1.The frequency of IL-23R rs6682925 T/C locus genotype distribution was statistically significant between the acute coronary syndrome group and the control group(the results were:χ2=9.858,P=0.007).In addition,the T and C allele frequencies of the IL-23R rs6682925 T/C locus were also statistically significant between the ACS group and the control group(the result wasχ2=10.833,P=0.001),C allele The frequency increased in the ACS group(results were 52.2%and 37.2%).IL-23R rs6682925 T/C locus genotype ratio and allele frequency,there was a statistically significant difference between the unstable angina group and the control group(P=0.039<0.05;P=0.008<0.05),the difference between the myocardial infarction group and the control group was also statistically significant(P=0.014<0.05;P=0.002<0.05).The CC genotype of IL-23R rs6682925 was associated with ACS genetic susceptibility(OR=3.261,95%CI:1.553~6.847,P=0.002).Compared with the control group,the risk of CC genotype carriers may develop into acute coronary syndrome is 3.261 times that of the TT genotype.In addition,the C allele of the IL-23R rs6682925 SNP locus was associated with susceptibility to ACS(OR=1.833,95%CI:1.268 to 2.650,P=0.001).The CC genotype of IL-23R rs6682925 was associated with susceptibility to unstable angina and myocardial infarction(OR=3.035,95%CI:1.298~7.097,P=0.010;OR=3.492,95%CI:1.511~8.072,P=0.003).2.The CC genotype of IL-23R rs6682925 was associated with susceptibility to three coronary vasculopathy(OR=4.676,95%CI:1.869~11.697,P=0.001).3.To analyze the association between IL-23R rs6682925 T/C polymorphism and coronary stenosis in patients with acute coronary syndrome,the results showed that there was no correlation between the degree of stenosis crown of patients with acute coronary syndrome and rs6682925 T/C site SNP(r_s=-0.70,P=0.345).4.The serum sIL-23R concentration in patients with ACS was significantly higher than that in the control group(353.20 pg/mL vs 187.41 pg/mL).The same analysis showed that the serum sIL-23R concentration in patients with unstable angina and myocardial infarction was also significantly higher than that in the control group(348.18 pg/).mL VS 187.41 pg/mL;358.23 pg/mL VS 187.41 pg/mL).5.Among the ACS patients,there was no significant difference between the sIL-23R concentrations of TC and CC genotype compara to TT genotypes(366.19 pg/mL vs317.53 pg/mL;363.40 pg/mL vs 317.53 pg/mL).Conclusion 1.IL-23R rs6682925 T/C gene polymorphism is associated with genetic susceptibility to acute coronary syndrome.The CC genotype may be a risk factor for acute coronary syndrome.The IL-23R rs6682925 gene polymorphism is associated with the genetic susceptibility between unstable angina and genetic myocardial infarction.CC genotype may be a risk factor for unstable angina and myocardial infarction.2.The IL-23R rs6682925 gene polymorphism is associated with genetic susceptibility between three-vessel disease in ACS patients.CC genotype may be a risk factor for three coronary vasculopathy in ACS patients.There was no correlation between the IL-23R rs6682925 T/C polymorphism and the degree of coronary artery stenosis in patients with ACS,which was not associated with ACS severity.3.Serum sIL-23R concentrations were significantly higher in the ACS group(and its clinical subgroups:UA and MI groups)than in the control group.IL-23R may amplify the inflammatory response by activating the IL-23/Th17 inflammatory pathway.High concentrations of serum sIL-23R may be a marker of AS inflammatory response activation in patients with ACS.4.There was no statistically significant difference in serum sIL-23R concentration between different genotypes of IL-23R rs6682925 SNP locus.Which means that the IL-23R rs6682925T/C polymorphism did not affect the expression of serum sIL-23R. |
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