학술논문
MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults.
Document Type
Academic Journal
Author
Bennett DA; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Parish S; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Millwood IY; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Guo Y; Fuwai Hospital Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Beijing, China.; Chen Y; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Turnbull I; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Yang L; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Lv J; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.; Yu C; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.; Davey Smith G; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Wang Y; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Wang Y; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; Peto R; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Collins R; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Walters RG; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Li L; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.; Chen Z; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Clarke R; Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 7802871 Publication Model: Print Cited Medium: Internet ISSN: 1464-3685 (Electronic) Linking ISSN: 03005771 NLM ISO Abbreviation: Int J Epidemiol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which increases plasma homocysteine (tHcy) levels, could clarify the causal relevance of elevated tHcy levels for stroke, ischaemic heart disease (IHD) and other diseases in populations without folic acid fortification.
Methods: In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for MTHFR and 12 240 developed a stroke during the 12-year follow-up. Logistic regression was used to estimate region-specific odds ratios (ORs) for total stroke and stroke types, IHD and other diseases comparing TT genotype for MTHFR C677T (two thymine alleles at position 677 of MTHFR C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting.
Results: Overall, 21% of participants had TT genotypes, but this varied from 5% to 41% across the 10 study regions. Individuals with TT genotypes had 13% (adjusted OR 1.13, 95% CI 1.09-1.17) higher risks of any stroke [with a 2-fold stronger association with intracerebral haemorrhage (1.24, 1.17-1.32) than for ischaemic stroke (1.11, 1.07-1.15)] than the reference CC genotype. In contrast, MTHFR C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease.
Conclusions: In Chinese adults, the MTHFR C677T polymorphism was associated with higher risks of stroke. The findings warrant corroboration by further trials of folic acid and implementation of mandatory folic acid fortification programmes for stroke prevention in low-folate populations.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Methods: In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for MTHFR and 12 240 developed a stroke during the 12-year follow-up. Logistic regression was used to estimate region-specific odds ratios (ORs) for total stroke and stroke types, IHD and other diseases comparing TT genotype for MTHFR C677T (two thymine alleles at position 677 of MTHFR C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting.
Results: Overall, 21% of participants had TT genotypes, but this varied from 5% to 41% across the 10 study regions. Individuals with TT genotypes had 13% (adjusted OR 1.13, 95% CI 1.09-1.17) higher risks of any stroke [with a 2-fold stronger association with intracerebral haemorrhage (1.24, 1.17-1.32) than for ischaemic stroke (1.11, 1.07-1.15)] than the reference CC genotype. In contrast, MTHFR C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease.
Conclusions: In Chinese adults, the MTHFR C677T polymorphism was associated with higher risks of stroke. The findings warrant corroboration by further trials of folic acid and implementation of mandatory folic acid fortification programmes for stroke prevention in low-folate populations.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)