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

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.