Association of Fibrinogen Beta Chain (FGB) rs1800790 and ITGB3 rs5918 gene variants with coagulation and ınflammation parameters according to sex in COVID-19 patients.
Jul 2026· Journal of Thrombosis and Thrombolysis· 0 citations· 23 references
Medicine
TL;DR
The combined influence of sex and coagulation-related genetic variants on thrombo-inflammatory patterns in COVID-19 patients highlights the potential clinical importance of considering sex-genotype interactions when evaluating thrombo-inflammatory responses and may contribute to more personalized risk assessment and management strategies in patients with COVID-19.
Hereditary protein C deficiency, caused by pathogenic variants in the PROC gene, is a known risk factor for venous thrombosis. However, data on PROC variants in Asian populations are limited. This study evaluated the clinical relevance of rs146922325 and its association with thrombotic outcomes in Taiwanese patients. Using genotyping data from a single-nucleotide polymorphism array as part of the Taiwan Precision Medicine Initiative, we conducted a retrospective case–control study that included 805 carriers of the PROC rs146922325 variant and 8,050 age- and sex-matched non-carriers. The baseline characteristics, coagulation profiles, and thrombotic outcomes were systematically compared. Univariable and multivariable logistic regression analyses were performed to assess the association between rs146922325 and venous thrombosis. Sensitivity analyses were conducted by restricting the cohort to warfarin-naïve participants and incident venous thrombosis events occurring after genotyping. Carriers of the rs146922325 T allele exhibited significantly lower protein C levels than non-carriers (71.28% vs. 114.58%, p < 0.001) and a higher prevalence of venous thrombosis (4.10% vs. 2.48%; p = 0.009). After multivariable adjustment, rs146922325 carrier status remained independently associated with an increased risk of venous thrombosis (adjusted odds ratio [aOR], 1.61; p = 0.015). Allelic analysis further indicated that the T allele was associated with elevated thrombotic risk (aOR, 1.74; p = 0.004). No clear dose–response pattern was observed because of the limited number of homozygous TT individuals. Sex-stratified analyses suggested a similar association across sexes; however, the sex × genotype interaction was not statistically significant. The PROC rs146922325 variant was associated with an increased risk of venous thrombosis in the Taiwanese population. These findings expand the current knowledge of PROC-related thrombophilia in East Asians and support the potential value of genetic risk stratification in thrombosis research.
Chi-Yen Chen, I-Chieh Chen, Guan-Cheng Lin et al.· Blood Research· 0 citations
COVID-19 is characterized by diffuse alveolar damage (COVID-19-DAD). The COVID-19-associated hemostatic alterations manifested by venous and arterial thrombosis deserve special attention. The issue is especially urgent for patients with diabetes mellitus. An observational study aimed to assess the role of polymorphisms of the genes ITGB3, ITGA2, and GP1BA in aggregation alteration in patients having COVID-19-DAD combined with type 2 diabetes mellitus (T2D). The control group included healthy volunteers (group 1; n = 22). Patients with COVID-19-DAD were divided into two group based on the fact of having or not having T2D: group 2 with no T2D (n = 52) and group 3 with T2D (n = 56). Platelet aggregation was assessed with the ALAT-2 laser platelet aggregation analyzer; adenosine diphosphate (ADP) at a concentration of 2.5 µg/mL, collagen 2.0 µg/mL, adrenaline 5 µg/mL, and ristomycin 7.5 mg/mL were used as aggregation inducers. In patients with СOVID-19-DAD and T2D, the rate of aggregate formation with the ADP induction was higher in carriers of the Т/С and С/С variants compared to carriers of the Т/Т variant – by 14 and 23% based on the median (р < 0.05). Polymorphisms were determined by polymerase chain reaction in buccal epithelial scrapings. In the group of patients with СOVID-19-DAD having no T2D, depending on the ITGA2 gene rs1126643 polymorphism the collagen-induced platelet aggregation is accelerated with the С/Т and Т/Т variants compared to the С/С variant — by 55 and 49%, respectively (р < 0.05); among individuals with СOVID-19-DAD and T2D, carriers of the Т/Т variant show the rate of the collagen-induced platelet aggregation 30% higher compared to carriers of the С/С variant (р < 0.05). Conclusion: in patients with COVID-19-DAD and T2D, the presence of the mutant allele Т of the ITGA2 gene rs1126643 polymorphism and allele С of the ITGB3 gene rs5918 polymorphism increases the rate of the collagen- and ADP-induced platelet aggregation.
M. Osikov, V. Antonov, S. Zotov· Bulletin of Russian State Me...· 0 citations
Purpose of the study. To evaluate the interaction of polymorphic variants rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu) of the β2-adrenoreceptor (β2-AR) gene with the development of liver cirrhosis (LC). Materials and methods. A total of 137 patients with liver cirrhosis and 143 healthy volunteers, who were Caucasian and unrelated to each other, participated in the observational case-control study. Genotyping of polymorphic variants Arg16Gly and Gln27Glu of the β2-AR gene was performed using the polymerase chain reaction (PCR) method by analyzing restriction fragment length polymorphism of amplicons (PDRF analysis). Results. Genotypes AG, GG and AA of the Arg16Gly polymorphism and genotypes CG, CC and GG of the Gln27Glu polymorphism of the β2-AR gene are not predictors of LC development (OR = 0.86; 95% CI: 0.53-1.37; p=0.52; OR=0.88; 95% CI:0.55-1.41; p=0.59; OR=1.81; 95% CI:0.91-3.62; p=0.09; OR=0.74; 95% CI:0.46-1.19; p=0.22; OR=1.55; 95% CI:0.93-2.58; p=0.09; OR=0.91; 95% CI: 0.52-1.57, p=0.72, respectively, p>0.05). Carrying the Arg16Arg/Gln27Gln haplotype increased the chance of developing LC by 2,4-fold (OR=2.42; 95%DI:1.13-5.18; p=0.02). Arg16ArgGln27Gln haplotype is associated with LC severity according to Child-Pugh classification (χ2=3.27; p=0.007) and severity of liver fibrosis according to APRI index (χ2=4.46; p=0.03). Conclusion. Haplotype Arg16ArgGln27Gln of β2-AR gene is a predictor of LC development, increasing the risk of disease development 2,4 times.
A. V. Molchanova, E. I. Mikhailova, A. Kalinin et al.· Experimental and Clinical Ga...· 0 citations
OBJECTIVES
Polycystic ovary syndrome (PCOS) is a complicated endocrine condition that causes ovarian dysfunction, metabolic problems, and hormonal irregularities. Genetic factors profoundly affect its pathogenesis. This study investigates the association between polymorphisms in the Transforming Growth Factor Alpha (TGFA) gene, specifically rs11466297 and rs3732248, and the risk of PCOS.
METHODS
We conducted a case-control study involving 200 individuals confirmed to have PCOS and 200 control subjects. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Amplification Refractory Mutation System (ARMS-PCR) procedures to genotype the TGFA SNPs rs11466297 A/C and rs3732248 G/A. We performed statistical analyses, including odds ratios (OR) and 95% confidence intervals (CI), to evaluate the relationship between the polymorphisms and the risk of PCOS.
RESULTS
Genotypic analysis revealed that the TGFA rs3732248 GA heterozygote was significantly associated with increased PCOS risk under the codominant model (OR = 2.16, 95% CI: 1.39-3.32, p < 0.001), dominant model (OR = 1.77, 95% CI: 1.18-2.65, p = 0.013), and overdominant model (OR = 2.26, 95% CI: 1.47-3.45, p = 0.001). All associations remained significant after Bonferroni correction (p < 0.025). For rs11466297, no significant association survived correction. PCOS patients had significantly higher BMI, waist circumference, total cholesterol, and triglycerides compared to controls (p < 0.001 for all). Haplotype analysis revealed no significant association between TGFA haplotypes and PCOS risk.
CONCLUSION
This study is the first to demonstrate that the TGFA rs3732248 polymorphism is significantly associated with PCOS susceptibility in an Iranian population. These findings provide novel genetic evidence supporting a role for TGFA in PCOS pathogenesis and warrant replication in larger independent cohorts.
F. Keykha, M. Mohammadi, Marzieh Ghasemi et al.· BMC Women's Health· 0 citations
AIMS
This study investigated the association between BAFF gene polymorphisms (rs1041569 and rs9514828) and preeclampsia (PE) susceptibility in an Iranian population, with a focus on disease severity and onset timing.
PATIENTS AND METHODS
This case-control study included 560 pregnant women (280 with PE and 280 normotensive controls) from Zahedan, southeastern Iran. Genotyping was performed using PCR-RFLP. Associations were assessed using logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS
For rs9514828, the CT and TT genotypes were associated with increased PE risk (OR = 1.81, p = 0.011; OR = 2.13, p = 0.002). For rs1041569, the AT and TT genotypes were also associated with increased risk (OR = 1.48, p = 0.033; OR = 1.68, p = 0.037). Haplotype analysis revealed that the C-A haplotype was protective (OR = 0.69, p = 0.003), while the T-T haplotype showed similar protection (OR = 0.69, p = 0.003). All genotype distributions were in Hardy-Weinberg equilibrium in the control group.
CONCLUSION
BAFF polymorphisms are significantly associated with PE susceptibility in the Iranian population and may serve as potential biomarkers for PE risk assessment.
Kosar Shirvani Baghbabouie, D. Jahantigh, F. Forghani et al.· Personalized Medicine· 0 citations