Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis
We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studie...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14641 |
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| author | Paul R. J. Ames Alessia Arcaro Matilde Caruso Maria Graf Vincenzo Marottoli Fabrizio Gentile |
| author_facet | Paul R. J. Ames Alessia Arcaro Matilde Caruso Maria Graf Vincenzo Marottoli Fabrizio Gentile |
| author_sort | Paul R. J. Ames |
| collection | DOAJ |
| description | We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (<i>p</i> = 0.001) with wide heterogeneity (<i>I</i><sup>2</sup> = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles <i>n</i> = 1, USA <i>n</i> = 5) yielded a neutral effect size, four (India <i>n</i> = 1, Arab countries <i>n</i> = 3) favoured SCD (<i>p</i> < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, <i>p</i> = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, <i>p</i> = 0.47); removal of one paediatric study yielded a significant effect size (<i>p</i> = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS. |
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| language | English |
| last_indexed | 2024-03-09T17:46:09Z |
| publishDate | 2022-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-137a237b870242b8a2f53dfb43197df72023-11-24T11:05:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231464110.3390/ijms232314641Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-AnalysisPaul R. J. Ames0Alessia Arcaro1Matilde Caruso2Maria Graf3Vincenzo Marottoli4Fabrizio Gentile5Immune Response and Vascular Disease Unit, Centro de Estudos de Doenças Crónicas, Universidade Nova de Lisboa, 1150-082 Lisbon, PortugalDepartment of Medicine & Health Sciences ‘V. Tiberio’, Università del Molise, 86100 Campobasso, ItalyTransfusion Medicine Unit, Cardarelli Hospital, 86100 Campobasso, ItalyImmunohaematology and Transfusion Medicine Unit, Department of Laboratory and Transfusion Medicine, Federico II University Hospital, 80131 Napoli, ItalyMultimedica Srl, 80134 Naples, ItalyDepartment of Medicine & Health Sciences ‘V. Tiberio’, Università del Molise, 86100 Campobasso, ItalyWe evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (<i>p</i> = 0.001) with wide heterogeneity (<i>I</i><sup>2</sup> = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles <i>n</i> = 1, USA <i>n</i> = 5) yielded a neutral effect size, four (India <i>n</i> = 1, Arab countries <i>n</i> = 3) favoured SCD (<i>p</i> < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, <i>p</i> = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, <i>p</i> = 0.47); removal of one paediatric study yielded a significant effect size (<i>p</i> = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.https://www.mdpi.com/1422-0067/23/23/14641homocysteinemethylenetetrahydrofolate reductaseMTHFR TT genotypesickle cell diseasevaso-occlusive crisisischemic stroke |
| spellingShingle | Paul R. J. Ames Alessia Arcaro Matilde Caruso Maria Graf Vincenzo Marottoli Fabrizio Gentile Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis International Journal of Molecular Sciences homocysteine methylenetetrahydrofolate reductase MTHFR TT genotype sickle cell disease vaso-occlusive crisis ischemic stroke |
| title | Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis |
| title_full | Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis |
| title_fullStr | Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis |
| title_short | Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis |
| title_sort | relevance of plasma homocysteine and methylenetetrahydrofolate reductase 677tt genotype in sickle cell disease a systematic review and meta analysis |
| topic | homocysteine methylenetetrahydrofolate reductase MTHFR TT genotype sickle cell disease vaso-occlusive crisis ischemic stroke |
| url | https://www.mdpi.com/1422-0067/23/23/14641 |
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