MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults
<p><strong>Background</strong></p> <p>The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the <i>methylenetetrahydrofolate reductase</i> (<i>MTHFR</i>) C677T polymorphism,...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2023
|
| _version_ | 1826312956347940864 |
|---|---|
| author | Bennett, DA Parish, S Millwood, IY Guo, Y Chen, Y Turnbull, I Yang, L Lv, J Yu, C Davey Smith, G Wang, Y Wang, Y Peto, R Collins, R Walters, RG Li, L Chen, Z Clarke, R |
| author2 | China Kadoorie Biobank (CKB) Study Collaborative Group |
| author_facet | China Kadoorie Biobank (CKB) Study Collaborative Group Bennett, DA Parish, S Millwood, IY Guo, Y Chen, Y Turnbull, I Yang, L Lv, J Yu, C Davey Smith, G Wang, Y Wang, Y Peto, R Collins, R Walters, RG Li, L Chen, Z Clarke, R |
| author_sort | Bennett, DA |
| collection | OXFORD |
| description | <p><strong>Background</strong></p>
<p>The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the <i>methylenetetrahydrofolate reductase</i> (<i>MTHFR</i>) 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.</p>
<p><strong>Methods</strong></p>
<p>In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for <i>MTHFR</i> 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 <i>MTHFR</i> C677T (two thymine alleles at position 677 of <i>MTHFR</i> C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting.</p>
<p><strong>Results</strong></p>
<p>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, <i>MTHFR</i> C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease.</p>
<p><strong>Conclusions</strong></p>
<p>In Chinese adults, the <i>MTHFR</i> 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.</p> |
| first_indexed | 2024-03-07T08:09:27Z |
| format | Journal article |
| id | oxford-uuid:5537bb56-f22d-4718-a3a5-b48b5f0de5b3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:05:04Z |
| publishDate | 2023 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:5537bb56-f22d-4718-a3a5-b48b5f0de5b32024-05-22T08:07:19ZMTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adultsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5537bb56-f22d-4718-a3a5-b48b5f0de5b3EnglishSymplectic ElementsOxford University Press2023Bennett, DAParish, SMillwood, IYGuo, YChen, YTurnbull, IYang, LLv, JYu, CDavey Smith, GWang, YWang, YPeto, RCollins, RWalters, RGLi, LChen, ZClarke, RChina Kadoorie Biobank (CKB) Study Collaborative Group<p><strong>Background</strong></p> <p>The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the <i>methylenetetrahydrofolate reductase</i> (<i>MTHFR</i>) 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.</p> <p><strong>Methods</strong></p> <p>In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for <i>MTHFR</i> 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 <i>MTHFR</i> C677T (two thymine alleles at position 677 of <i>MTHFR</i> C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting.</p> <p><strong>Results</strong></p> <p>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, <i>MTHFR</i> C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease.</p> <p><strong>Conclusions</strong></p> <p>In Chinese adults, the <i>MTHFR</i> 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.</p> |
| spellingShingle | Bennett, DA Parish, S Millwood, IY Guo, Y Chen, Y Turnbull, I Yang, L Lv, J Yu, C Davey Smith, G Wang, Y Wang, Y Peto, R Collins, R Walters, RG Li, L Chen, Z Clarke, R MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults |
| title | MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults |
| title_full | MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults |
| title_fullStr | MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults |
| title_full_unstemmed | MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults |
| title_short | MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults |
| title_sort | mthfr and risk of stroke and heart disease in a low folate population a prospective study of 156 000 chinese adults |
| work_keys_str_mv | AT bennettda mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT parishs mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT millwoodiy mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT guoy mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT cheny mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT turnbulli mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT yangl mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT lvj mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT yuc mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT daveysmithg mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT wangy mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT wangy mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT petor mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT collinsr mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT waltersrg mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT lil mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT chenz mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults AT clarker mthfrandriskofstrokeandheartdiseaseinalowfolatepopulationaprospectivestudyof156000chineseadults |