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Objective:To study the relationship between isolated systolic hypertenson and MTHFR,CBS the keys enzyme of homocysteine metabolism,gene polymorphisms,related variation of homocysteine level,their metabolic factors,so as to screen the predisposing gene and intermediate phenotype of ISH.Methods:From Tianjin hypertension prevention and cure area selected by examinations to get 55 examples,matched control 46 example,apply the molecular biology method to detect MTHFR C677,CBS G919,T833,C341 different site gene polymorphisms,and measurese the concentration of Hcy,folic acid,vitamin B12 and B6 at the same time,then proceed the relativity analysis.Results:The genotype frequency of ISH group is different from that of control group(P＜0.05).The higher frequency of T allele of MTHFR is 69.1%,observed in ISH group(P＜0.01); and the mutation allelt frequency of CBS is 15.2%,different from matched control.The Hcy levels of ISH group(17.7±8.5μmol s/l)are higher than those of matched control(10.65±3.1μmol s/l,P＜0.05).But the concentration of folic acid,vitamin B12 and B6 are lower compared to the controlled(P＜0.05).There are more hyperhomocysteinemia patients in ISH group(P＜0.05). Plasma homocyeteine play apernicious role in ISH pathogeine and folic acid may have negative effect on ISH.Conclusion:Mutation of MTHFR or CBS can both cause the elevation of plasma homocysteine so as to boost the onset of ISH.Then we can draw the conclusion that MTHFR and CBS genes may be the predisposing gene of ISH,Hcy my be the improtant intermiediate phenotype.Reasonable complementation of folic acid,vitamin B6,vitaminB12 can lower the plasma Hcy level,and defer ISH occurrence and progress.