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Earlier onset of peripheral arterial thrombosis in homozygous MTHFR C677T carriers than in other MTHFR genotypes: a cohort study

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Abstract

To investigate whether age at first presentation of pure peripheral arterial thrombosis (PAT) in lower and upper limbs and in the splanchnic circulation occurs earlier in carriers of the methylenetetrahydrofolate reductase (MTHFR) T677T genotype compared to the heterozygous and wild type and to identify predictors of a possible earlier onset. Retrospective cohort study on 27 MTHFR TT, 29 MTHFR TC and 29 MTHFR CC participants; data regarding age, sex, age at PAT, clinical history (dyslipidaemia, hypertension, smoking, obesity) and homocysteine (HC) measured by immunoassay were collected. Age at PAT was lower in MTHFR TT than MTHFR TC and CC (43 ± 9 vs 47 ± 9 vs 51 ± 4 years, respectively, p = 0.02); plasma HC was higher in MTHFR TT than in the other groups (25 ± 19 vs 12.7 ± 6.7 vs 11.3 ± 3.3 μmol/l, respectively, p < 0.001) while the activated partial thromboplastin ratio (aPTTr) was lower in MTHFR TT than in other genotypes (0.90 ± 0.10 vs 0.97 ± 0.12 vs 0.97 ± 0.08 μmol/L p < 0.001). Among categorical variables, MTHFR TT and dyslipidaemia independently predicted age at AT (p = 0.01 & p = 0.03, respectively) whereas among the continuous variables HC independently predicted age at PAT (p = 0.02) as well as the aPTTr (p = 0.001); smoking predicted lower limb PAT (p = 0.005). MTHFR TT carriers develop their first PAT an average of 4 and 8 years earlier than MTHF CT and CC genotypes; MTHFR TT, dyslipidaemia and plasma HC contribute to the prematurity of the PAT while the interplay between elevated HC and smoking may affect type of arterial district occlusion.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Immune Response and Vascular Disease Unit, CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal

    Paul R. J. Ames

  2. Dumfries and Galloway Royal Infirmary, Cargenbridge, Dumfries, DG2 8RX, Scotland, UK

    Paul R. J. Ames

  3. Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

    Giovanna D’Andrea & Maurizio Maraglione

  4. Multimedica Srl, Naples, Italy

    Vincenzo Marottoli & Luigi Iannaccone

  5. Department of Medicine and Health Sciences’V. Tiberio’, University of Molise, Campobasso, Italy

    Alessia Arcaro & Fabrizio Gentile

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  1. Paul R. J. Ames
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  2. Giovanna D’Andrea
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  3. Vincenzo Marottoli
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  4. Alessia Arcaro
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  6. Maurizio Maraglione
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  7. Fabrizio Gentile
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Contributions

All authors contributed to the study conception and design. Material preparation and analysis were performed by Giovanna D’Andrea, Luigi Iannaccone and Alessia Arcaro; data collection was performed by Paul RJ Ames, Vincenzo Marottoli and Fabrizio Gentile; statistical analysis was performed by Paul RJ Ames and Maurizio Margaglione; the first draft of the manuscript was written by Maurizio Margaglione, subsequently reviewed by all authors and finalized by Paul RJ Ames. All authors read and approved the final manuscript.

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Correspondence to Paul R. J. Ames.

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None of the authors has any relevant financial or non-financial interests to disclose.

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At the time of the original study, patients gave informed and written consent to the use and storage of their genetic material and of their anonymized clinical information as per approval of the local Ethics Committee. At the time of the original study, patients gave informed and written consent to the use and storage of their genetic material and of their anonymized clinical information as per approval of the local Ethics Committee.

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Ames, P.R.J., D’Andrea, G., Marottoli, V. et al. Earlier onset of peripheral arterial thrombosis in homozygous MTHFR C677T carriers than in other MTHFR genotypes: a cohort study. Clin Exp Med 23, 503–509 (2023). https://doi.org/10.1007/s10238-022-00819-y

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  • DOI: https://doi.org/10.1007/s10238-022-00819-y

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