The Correlation Study Of CX3CR1 Polymorphisms And Ischemic Cerebrovascular Disease

ObjectiveThe aim of this study was to evaluate the relationship between chemokine receptor CX3CR1 and ischemic cerebrovascular disease(ICVD) by searched the expression of CX3CR1 polymorphism in ICVD, and was to indicate association the expression levels of plasma sequestered chemokine fractalkine(sFkn) with acute cerebral infarction by examined the level of sFkn among patients with acute cerebral infarction,which provide the theoretical basis for ischemic cerebrovascular disease diagnosis and treatment.MethodsThis effect was observed both by a study involving 165 patients with ischemic cerebrovascular disease(ICVD) and 150 age- and sex-matched healthy controls by a standard salting-out procedure.To analyze V249I and T280M polymorphisms distribution in both groups and the relation V249I and T280M polymorphisms to blood pressure,blood glucose and metabolism of blood-fat index.The polymorphisms of CX3CR1 were analyzed by multiplex polymerase chain reaction -restriction fragment length based (PCR-RFLB). 40 acute cerebral infarction patients'plasma was serially obtained after attacking 1,3,7 and 14 day. The control subjects'blood was collected only once. We also analyzed the association between the level of sFkn and different patients according to the clinical nerve deficiency scale. sFkn levels in plasma samples were determined with ELISA method using human fractalkine immunoassay kit.Results1. The frequency of I249 allele and M280 allele were 6% and 2.3% in Han population of Changsha area,Hunan province .There were significant differences in the distribution of CX3CR1 between Han population of Changsha area in Hunan province and Uygur population as well as European population. That is, I249 allele and M280 allele of Han population of Changsha area in Hunan province were higher than Uygur population and European population. The distribution of CX3CR1 polymorphism of Han population of Changsha area in Hunan province were similar to that of Han population in Xinjiang Uygur autonomous region,Chinese Dai population,Chingpaw population and Japanese population.2. There were significant differences between cerebrovascular disease group and control group in CX3CR1 distribution.The frequency of I249 allele in Ischemic ICVD patients(13.9%)was significantly higher than that in controls(6%),and the odds ratios was 4.033,and 95% confidence interval was 1.739～9.350. The frequency of M280 allele in Ischemic ICVD patients(8.7%)was higher than that in controls(2.3%),and the odds ratios was 2.538,and 95% confidence interval was 1.436～4.484. There were no differences in CX3CR1 polymorphisms among different ICVD subtypes(P>0.05)3. The CX3CR1 Polymorphism might not be associated with blood pressure,blood glucose and metabolism of blood-fat index. (P>0.05).4. There were Linkage disequlibrium between V249I allele and T280M allele,and Linkage disequilibrium factor was 0.965.5.There was statistically significant difference in the plasma levels of sFkn between CI group and control group (P<0.05).On the 1st, 3rd, 7th and 14th days after admission, the level of sFkn was 1191.6±747.5pg/ml,1795.3±1204.7 pg/ml,2118.1±1180.3 pg/ml and 1035.7±461.1 pg/ml, and that of control group was 471.4±79.7 pg/ml.It began to increase at day 3,and peaked an day 7.The high level of sFkn lasted to day 14(P<0.05).6. Plasma sFkn content in severe group was significantly higher than that in mild and medium group(P<0.05). The level of plasma sFkn in medium group were higher than that in mild group, but there was no statistical significance. Patients with more severe type of cerebral infarction significantly increased The plasma sFkn levels in patients with acute cerebral infarction and clinical neurological defect score were positively correlated(r=0.768,P<0.05).Conclusions1. CX3CR1 allelic polymorphism distribution may have ethnic and regional differences, and Han population of Changsha area in Hunan provience may have its own unique genetic characteristic.2. The CX3CR1 polymorphisms may be associated with ischemic cerebrovascular disease.3. The polymorphism of the CX3CR1 may not be associated with blood pressure,blood glucose and metabolism of blood-fat index.4. The level of plasma sFkn may be positively correlated to the severity of the cerebral infarction.These data suggest that sFkn may be a new marker of inflammation in the cerebral infarction.