Correlation Of Homocysteine Concentration And MTHFR Gene Polymorphism With Vascular Dementia

Background and objectiveVascular Dementia(VaD) is a chronic progressive disease with cognitive impairment and persistent mental retardation, which caused by a variety of cerebrovascular diseases. It is the second most common type of dementia after Alzheimer's disease(AD). In China, the prevalence rate of VaD is from 1.1% to 3.0%. VaD increases the risk of death, reduces the quality of life, increases the cost of economy, which brings huge burden to the family and society. So in recent years, vascular dementia is becoming a hot research for scholars. VaD and stroke have some related risk factors, as age, sex, race, smoking, atherosclerotic vascular diseases, hypertension, diabetes, chronic atrial fibrillation, ypercholesterolemia, ect. The occurrence of VaD is not only directly related to cerebrovascular disease, but also is influenced by genetic and environmental factors. Clinical investigations and epidemiological studies found that hyperhomocysteinemia(HHcy) could prompte atherosclerotic diseases, and it could be a new independent risk factor for cerebrovascular diseases, and be related to the cognitive ability of patients. N5, N10- methylenetetrahydrofolate reductase(MTHFR) is the rate-limiting enzyme of Hcy metabolize and the C677 T mutation can cause HHcy. But the causes of VaD have not been fully elucidated. This article is aimed to investigate the correlation between VaD, plasma Hcy, and the impact of MTHFR C677 T point mutation on Hcy concentration, in order to identify the causes of relevant factors of VaD, and provide evidences for the prevention and treatment of VaD. Methods73 patients with VaD and 75 patients with nondemented cerebral infarction were recruited in this study. The circulating enzymatic method was used to test the Hcy concentration in plasma.The folic acid and vitamin B12 levels were measured by immunoassay method. The method of PCR-chip hybridization was used to analysis the polymorphism of MTHFR gene. And the scores of MMSE were used to assess the degree of dementia with the patients of VaD. Results1. The frequency(76.71%) of MTHFR gene homozygous mutation(TT) and heterozygous mutation(CT) in VaD group was significantly higher than non-dementia cerebral infarction group(69.33%, P<0.05), and T allele frequency(60.27%) was significantly higher than non-dementia cerebral infarction group(45.33%, P<0.05).2. The Hcy level in plasma of VaD group was significantly higher than non-dementia cerebral infarction group(P<0.001), the folate level was significantly lower than non-dementia cerebral infarction group(P<0.001), and the vitamin B12 level of VaD group was significantly lower than non-dementia cerebral infarction group( P<0.05).3. The Hcy levels in plasma of patients from moderate dementia group and severe dementia group were significantly elevated than mild dementia group(P<0.05); the Hcy level in plasma of patients with severe dementia group was significantly higher, compared with moderate dementia group(P<0.05); by the correlation analysis of Hcy levels in plasma and the MMSE scores of VaD patients showed negatively correlated(r =-0.475, P<0.05).4. The Hcy level in plasma of individualsion two groups with MTHFR gene TT genotype was significantly higher than CT and CC genotype(both P<0.001); the Hcy levesl in plasma of individuals with CT genotype compared with CC genotype were significantly different(P<0.001), the result of Hcy concentration in each group was found in the following genetype(from higher to lower): TT> CT> CC(all P<0.001). ConclusionsThe high Hcy level in plasma is one of the risk factors for VaD. The correlation between plasma Hcy level and folic acid, vitamin B12 was negatived. The deficiency of folic acid and vitamin B12 may lead to higher Hcy level in plasma. MTHFR gene mutation may cause higher Hcy level in plasma. The high Hcy level in plasma is one of the factors for the severity of VaD.