Association Of Paraoxonase-1 Gene Polymorphism With Susceptibility To Cerebral Infarction And Short-term Prognosis

Objective:The purpose of this study was to investigate the relationship between the single nucleotide polymorphism(SNP)of paraoxonase-1(PON-1)gene and the susceptibility and short-term prognosis of cerebral infarction(CI),and to explore the influencing factors of the onset and short-term prognosis of cerebral infarction at the gene level,so as to provide a theoretical basis for gene diagnosis,treatment selection and gene targeted therapy of cerebral infarction patients.Methods:1.In the Affiliated Hospital of Youjiang Medical College for nationalities,we collected 136 patients with cerebral infarction who met the diagnostic criteria of"China guidelines for diagnosis and treatment of acute ischemic stroke 2018"as the case group,and 150 age-matched and gender matched healthy people without cerebrovascular disease as the control group.The patients were divided into subgroups according to the situation of vascular stenosis.The patients with cerebral vascular stenosis>50%were divided into large artery atherosclerotic cerebral infarction group(large artery atherosclerotic cerebral infarction group,LAA group).The patients with cerebral vascular stenosis less than or equal to 50%were classified as non atherosclerotic cerebral infarction group(non LAA group).After 90 days of onset,the patients were followed up by telephone for m RS score,m RS score>2 were classified as poor prognosis group,and≤2 were classified as good prognosis group.2.Peripheral blood samples were collected and DNA was extracted.The target gene fragment was extended by snapshot method,the product information was analyzed by genemarker to determine the Q192R genotype of PON-1 gene.Chi square test confirmed that the genotype distribution frequency of the samples was in accordance with Hardy Weinberg equilibrium.A case-control study was conducted to analyze the frequency distribution of Q192R genotype of PON-1 gene between case group and control group,LAA group and non LAA group,good prognosis group and poor prognosis group.Combined with clinical data,the related clinical data were analyzed by multivariate logistic regression.After excluding confounding factors,the risk genotype to the susceptibility of cerebral infarction,vascular stenosis and prognosis were analyzed.The test level was p<0.05.Results:(1)The results ofχ~2test showed that the P values of the selected subjects were all greater than 0.05,means that the distribution of genotypes conformed to Hardy Weinberg’s law of genetic equilibrium,and the selected samples were representative.(2)There was no significant difference in the frequency of genotype distribution between the case group and the control group(χ~2=3.379,P=0.185).The frequency of R allele was 65.44%in the case group and 57.33%in the control group,χ~2=3.949,P=0.047,OR=1.409,suggesting that the allele is associated with the onset of cerebral infarction.(3)The distribution of PON-1 gene Q192R genotype was different between LAA group and non LAA group.The genotype frequencies of RR were 62.22%and38.46%respectively,the frequency of RR genotype was higher in LAA group,χ~2=6.840,P=0.033,the distribution of dominant model(RQ+QQ)/RR between the two groups was statistically different after the correction of diabetic history by logistic regression,P=0.009,OR=2.697.There were also significant differences in the distribution of R and Q alleles between LAA group and non LAA group,P=0.014,OR=2.023,RR genotype and R allele were associated with LAA cerebral infarction.(4)Single nucleotide polymorphism at Q192R site of PON-1 gene is associated with short-term prognosis of cerebral infarction.There were 98 patients with good prognosis and 38 patients with poor prognosis,the frequency of RR gene was 38 and25,respectively.Statistical test showed thatχ~2=8.218,P=0.016.The allele R frequencies were 118 and 60 in good prognosis group and poor prognosis group,χ~2=9.143,P=0.004,OR=2.479,RR genotype and R allele were associated with poor short-term prognosis in patients with cerebral infarction.Logistic regression analysis showed that RR genotype was an independent risk factor for poor short-term prognosis.Conclusion:(1)The Q192R polymorphism of PON-1 gene is associated with susceptibility to cerebral infarction.The R allele may be a risk factor for susceptibility to cerebral infarction and poor short-term prognosis of cerebral infarction.(2)RR genotype and R allele at Q192R site of PON-1 gene are risk factors of vascular stenosis in patients with cerebral infarction,RR genotype and R allele carriers are more likely to have cerebrovascular stenosis more than 50%,which can be used as a predictor of large atherosclerotic cerebral infarction.(3)The prognosis of patients with cerebral infarction with the R192R of PON-1is worse,RR genotype and R allele are independent risk factors for poor short-term prognosis of cerebral infarction.