Plasma thiol levels and methylenetetrahydrofolate reductase gene c.665C > T and c.1286A > C variants affect fibrin clot properties in Polish venous thromboembolic patients

Adrianna Klajmon; Rafał Głowacki; Justyna Piechocka; Piotr Kopiński; Michał Ząbczyk; Joanna Natorska

doi:10.1016/j.ymgme.2023.107623

Plasma thiol levels and methylenetetrahydrofolate reductase gene c.665C > T and c.1286A > C variants affect fibrin clot properties in Polish venous thromboembolic patients

Mol Genet Metab. 2023 Jul;139(3):107623. doi: 10.1016/j.ymgme.2023.107623. Epub 2023 Jun 2.

Authors

Adrianna Klajmon¹, Rafał Głowacki², Justyna Piechocka², Piotr Kopiński³, Michał Ząbczyk⁴, Joanna Natorska⁵

Affiliations

¹ John Paul II Hospital, 80 Prądnicka St., 31-202 Kraków, Poland.
² Faculty of Chemistry, Department of Environmental Chemistry, University of Lodz, 163 Pomorska St., 90-236 Łódź, Poland.
³ John Paul II Hospital, 80 Prądnicka St., 31-202 Kraków, Poland; Department of Lung Diseases, Cancer and Tuberculosis, Collegium Medicum, Nicolaus Copernicus University, 13/15 Jagiellońska St., 85-067 Bydgoszcz, Poland.
⁴ John Paul II Hospital, 80 Prądnicka St., 31-202 Kraków, Poland; Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St., 31-202 Kraków, Poland.
⁵ John Paul II Hospital, 80 Prądnicka St., 31-202 Kraków, Poland; Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St., 31-202 Kraków, Poland. Electronic address: joanna.natorska@uj.edu.pl.

PMID: 37302269
DOI: 10.1016/j.ymgme.2023.107623

Abstract

Background and aims: Aminothiols, including cysteine (Cys) and glutathione (GSH) in relation to fibrin clot phenotype were not investigated in patients with venous thromboembolism (VTE) and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene variants. We aimed to explore the associations between MTHFR variants and plasma oxidative stress indicators including aminothiols as well as fibrin clot properties with plasma oxidative status and fibrin clot properties in this group of patients.

Methods: In 387 VTE patients the MTHFR c.665C > T and c.1286A > C variants were genotyped, together with chromatographic separation of plasma thiols. We also determined nitrotyrosine levels and fibrin clot properties, including clot permeability (K_s), lysis time (CLT), and fibrin fibers thickness.

Results: There were 193 patients with MTHFR c.665C > T (49.9%) and 214 (55.3%) with c.1286A > C variants. Both allele carriers with total homocysteine (tHcy) levels >15 μM (n = 71, 18.3%), compared to patients with tHcy ≤15 μM had 11.5% and 12.5% higher Cys levels, 20.6% and 34.3% higher GSH levels as well as 28.1% and 57.4% increased nitrotyrosine levels, respectively (all P < 0.05). The MTHFR c.665C > T carriers with tHcy levels >15 μM compared to tHcy ≤15 μM had 39.4% reduced K_s and 9% reduced fibrin fibers thickness (both P < 0.05) with no differences in CLT. In the MTHFR c.1286A > C carriers with tHcy levels >15 μM, K_s was decreased by 44.5%, CLT prolonged by 46.1%, and fibrin fibers thickness was reduced by 14.5% compared to patients with tHcy ≤15 μM (all P < 0.05). Nitrotyrosine levels in MTHFR variants carriers correlated with K_s (r = -0.38, P < 0.05) and fibrin fibers diameter (r = -0.50, P < 0.05).

Conclusions: Our study indicates that patients with MTHFR variants and tHcy >15 μM are characterized by elevated Cys and nitrotyrosine levels associated with prothrombotic fibrin clot properties.

Keywords: Aminothiol compounds; Fibrin clot properties; Hyperhomocysteinemia; MTHFR variants; Redox status in plasma; VTE.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Fibrin / genetics
Homocysteine / genetics
Humans
Methylenetetrahydrofolate Reductase (NADPH2) / genetics
Poland
Sulfhydryl Compounds
Thrombosis*
Venous Thromboembolism*

Substances

Fibrin
Homocysteine
Methylenetetrahydrofolate Reductase (NADPH2)
Sulfhydryl Compounds
MTHFR protein, human