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P4‐108: MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly
Author(s) -
Pandey Pratima,
Pradhan Sunil,
Modi Dinesh R.,
Mittal Balraj
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.776
Subject(s) - methylenetetrahydrofolate reductase , vascular dementia , dementia , medicine , allele , odds ratio , apolipoprotein e , endocrinology , gastroenterology , disease , genetics , biology , gene
Background: Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, roles of angiotensin converting enzyme (ACE) and methylene tetrahydrofolate reductase (MTHFR) genes as putative risk factors, has been examined but the outcome of these studies have been inconclusive. Present study therefore attempted to see the importance of ACE alu Insertion/Deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. Methods: This study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCRRFLP method.Binary logistic regression analysis was used to find age adjusted odds ratio, using age as a covariate. All analyses were done using SPSS v 11.5. P value of less than 0.05 was taken as significant. Results: APOE E4 allele frequency was found to be significantly higher in degenerative dementia (p1⁄4 0.0001, OR 3.86, 95% CI 1.97-7.57) as well as vascular dementia patients (p1⁄40.004, OR 2.88, CI 1.39-5.95). The frequency of this allele was still high when we combined the two dementias (p1⁄4 0.0001, OR 3.39, CI 1.82-6.32).Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE*E4, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Conclusions: Observations in the present study again support the APOE E4 allele as a major risk factor in late onset sporadic dementia. However ACE I/D polymorphism is not a major contributory factor for either degenerative or vascular dementia; rather it might be playing a role in the primary ageing process either through the modulation of ischemia or through the effect on amyloid deposition. MTHFR gene polymorphism did not seem to play any role in the development of disease either alone, or in the presence of confounding factors.