The Association Analysis Of Plasma Hcy Level And MTHFR Gene Polymorphism With Ankylosing Spondylitis

Background:Homocysteine(Hcy)is the intermediate product of metabolism of modified DNA methylation,the abnormally increased plasma Hcy level is likely to increase the impact of DNA methylation process and thus affect the expression of certain genes and promoting the development of disease.Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in the conversion of Hcy,it plays an important role in folic acid and Hcy metabolism, DNA methylation and DNA synthesis.In vitro and in vivo studies show that chronic lack of folic acid or methyl relate to DNA methylation abnormalities and will cause DNA strand breaks,chromosome change of reorganization and abnormal chromosome separation.Research has revealed that: hyperhomocysteinemia can lead to low genomic DNA methylation,which evoked some autoimmune diseases.There is no report about patients with ankylosing spondylitis(AS)Hcy and genomic DNA methylation level of coverage.Objective:To investigate the relationship of plasma Hcy level to AS.To analyze the association between the MTHFR gene polymorphism and AS.To seek the potential pathogenesis of Hcy,MTHFR gene polymorphism and demethylation in AS.Methods:one hundred patients with AS and Sixty healthy controls were included in the study.The plasma Hcy level was examined by enzyme-linked immunoadsordent assay and MTHFR gene polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism (RFLP).The basis sequences of mutations were analyzed by DNA sequence analysis.Results:Compared with healthy controls,the plasma Hcy level in AS patients was significantly higher than controls(t′=14.121,P＜0.001).There was no significant difference in the frequencies of MTHFR C/C,C/T genetype between AS patients and the controls(X²_C/C=1.508,X²_C/T=0.067,P＞0.05). There was no significant difference in the frequencies of alleles between AS patients and the controls(X²=3.008,P＞0.05).But the frequencies of MTHFR T/T genetype was difference between AS patients and the controls(17%VS 5%,X²_{T/T=4.937,P＜0.05}.The plasma Hcy level of C/C,C/T and T/T genetype in AS patients was significantly higher than that of in the controls(t_C/C =8.042;t_C/T=8.315;t_T/T=9.450,P＜0.001).There was no significant difference in the plasma Hcy level of C/T and T/T genetype in AS patients and the controls(t=2.712,P＞0.05).The plasma Hcy level of T/T genetype was significantly higher than that of C/T or C/C genetype in AS patients and the controls(t=10.279,P＜0.001).Logistical-regression analysis indicated that Hcy was an independent risk factor for AS patients(P＜0.001,OR=4.582,95% CI=1.984—10.585).PCR product sequencing results confirmed the correctness of digestion type.Conclusion:The plasma Hcy were significantly increased in patients with AS,Hyperhomocysteinemia was an independent risk factor for AS.MTHFR T/T genetype mutation was an important influence mechanism of hyperhomocysteinemia and may be related with AS.Whether hyperhomocysteinemia could lead to low methylation of some DNA and Hcy could impact on the MTHFR gene-modified methylation of the promoter and the expression of mRNA,will further study in AS.