A Case-Control Study of Factor V Leiden G1691A and MTHFR A1298C Polymorphisms and Clinical Outcomes in Patients With COVID-19.

Publication date: Jul 01, 2026

The clinical relevance of inherited thrombophilia-related polymorphisms in COVID-19 remains uncertain. This study investigated the distribution of Factor V Leiden (FVL) G1691A and MTHFR A1298C polymorphisms in patients with COVID-19 and associations with laboratory findings and short-term mortality. This case-control study included 150 patients with PCR-confirmed COVID-19 and 300 controls. Genomic DNA was isolated from peripheral blood, and FVL G1691A and MTHFR A1298C polymorphisms were analyzed. Associations with d-dimer levels, hospitalization duration, and 30- and 90-day mortality were evaluated using multivariable linear and Cox regression analyses. The FVL GG genotype was less frequent in patients than controls (77. 3% vs. 87. 0%, p = 0. 009), whereas the MTHFR AA genotype was more frequent (76. 7% vs. 61. 3%, p = 0. 001). Heterozygosity in both genes did not differ between groups (8. 0% vs. 6. 3%, p = 0. 552). Patients with heterozygosity in both genes had higher d-dimer levels (median 435. 0 vs. 201. 0 ng/mL, p = 0. 024) and longer hospitalization (median 7. 5 vs. 5. 0 days, p = 0. 037). After adjustment, heterozygosity in both genes remained associated with higher log-transformed d-dimer levels (β = 0. 758, 95% CI: 0. 239-1. 277; p = 0. 005), as did MTHFR A1298C (β = 0. 432, 95% CI: 0. 007-0. 856; p = 0. 046). None of the polymorphisms was associated with 30- or 90-day mortality, while age independently predicted both outcomes. Thrombophilia-related polymorphisms may influence d-dimer levels and hospitalization duration in COVID-19 but do not appear to affect short-term mortality.

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Concepts Keywords
A1298c Adult
Genomic Aged
Hospitalization Betacoronavirus
Pcr Case-Control Studies
Thrombophilia case–control study
Coronavirus Infections
COVID-19
COVID‐19
d‐dimer
epidemiology
Factor V
Factor V
factor V Leiden
Factor V Leiden
Female
fibrin fragment D
Genotype
Humans
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
mortality
MTHFR
MTHFR protein, human
Pandemics
Pneumonia, Viral
Polymorphism, Single Nucleotide
SARS-CoV-2
Thrombophilia
thrombophilia

Semantics

Type Source Name
disease MESH COVID-19
disease MESH thrombophilia
disease MESH included
disease MESH Inflammation
disease MESH Emergency
disease MESH Viral pneumonia
disease MESH injury
disease MESH severe acute respiratory syndrome
disease MESH thromboembolism
pathway REACTOME Reproduction
drug DRUGBANK Beroctocog alfa
drug DRUGBANK Prothrombin
drug DRUGBANK Thrombin
disease MESH thrombosis
disease MESH atherosclerosis
disease MESH coronary artery disease
disease MESH myocardial infarction
disease MESH ischemic stroke
disease MESH cough
disease MESH fever
disease MESH pneumonia
disease MESH chronic disease
disease MESH infection
disease MESH chronic kidney disease
disease MESH liver disease
disease MESH thyroid disease
disease MESH asthma
pathway KEGG Asthma
disease MESH heart failure
disease MESH malignancy
disease MESH HRs
drug DRUGBANK Urea
drug DRUGBANK Creatinine
drug DRUGBANK Fibrinogen Human
disease MESH venous thromboembolism
pathway REACTOME Methylation
disease MESH genetic susceptibility
disease MESH Preeclampsia
disease MESH Leukemia
disease MESH Stroke
disease MESH Cerebrovascular Diseases
disease MESH Rieg
disease MESH Death
disease MESH Hos
disease MESH Coronavirus Infections

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