Association of the PROC rs146922325 variant with venous thrombosis in a Taiwanese population
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.