Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing body of evidence suggests that different genetic factors, such as angiotensin-converting enzyme (ACE) I/D, angiotensin II type-1 receptor (AT1R) A1166C, methylenetetrahydrofolate reductase (MTHFR) C677T and ENOS G894T variants are associated with an endothelial dysfunction (ED). EDs are relatively new phenomena that are presumed to contribute to vasoregulatory malfunctions at the small-vessel level. Ever more clinical observations indicate that the above genetic variants are also associated with cerebral small-vessel disorders. This article reviews the knowledge available on the roles of ED- associated genetic variants in cerebral circulatory disorders, and suggests that EDs can be causative factors for different common cerebral pathologies such as leukoaraiosis or/and small-vessel infarcts. Newly-developed drugs involving phosphodiesterase type-5 inhibitors, which improve the endothelial functions, may comprise a new approach to the treatment and prevention of small-vessel cerebral circulatory disorders.
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PMID:Genetic variant-associated endothelial dysfunction behind small-vessel cerebral circulatory disorders: a new pathomechanism behind common cerebral phenotypes. 1750 88

Previous studies have suggested that both angiotensin II type-1 receptor (AT1R) 1166C and methylenetetrahydrofolate reductase (MTHFR) 677T variants can have disadvantageous effects on the small-vessel circulation under certain conditions. The purpose of this study was to analyze the possible consequences of the simultaneous distribution of these two genetic variants in different types of ischemic stroke. The genetic and clinical data on 357 ischemic stroke patients and 263 control subjects were analyzed by using univariate and logistic statistical approaches. Neither the MTHFR 677T nor the AT1R 1166C genetic variant alone conferred the risk of any subtype of ischemic stroke. The combination of the homozygous MTHFR 677TT genotype and at least one AT1R 1166C allele occurred more frequently in the ischemic stroke patients (8.68%) than in the controls (4.56%, p < 0.05). Specific subclassification of the patients revealed an accumulation of this combination in small-vessel-associated ischemic stroke (12.2%, p < 0.01); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.66 (95% confidence interval, 1.28-7.89; p < 0.05). These findings suggest that the combination of these two genetic factors can contribute to the development of small-vessel cerebral infarcts. Although the exact mechanism of action is not known, addition of the unfavourable effects on the endothelial function can be presumed.
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PMID:The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke. 1772 26