Uncovering genetic risk: Protein C variants linked to deep venous thrombosis in Chinese population
image: Differences in the positive rate and allele frequency of the p.Lys193del mutation in DVT and control groups. DVT: deep venous thrombosis.
Credit: Xu-qian Wei, Xiao-lei Yi, Wei-bin Chen, Jin Tang, Jing Da.
This study, published in LabMed Discovery, explores the genetic basis of deep venous thrombosis (DVT) in the Chinese population, focusing specifically on mutations in the protein C (PROC) gene. DVT is a potentially life-threatening condition where blood clots form in the deep veins, often in the legs, and it remains a major contributor to morbidity and mortality worldwide. While Western populations frequently carry well-known thrombophilia risk mutations such as factor V Leiden and prothrombin G20210A, these are rare in East Asians. The authors aimed to identify more region-specific genetic markers by examining mutations in the PROC gene, which plays a critical role in the natural anticoagulant pathway.
The research was conducted as a retrospective observational case–control study at a single center. A total of 180 patients with confirmed DVT and 103 healthy controls were enrolled. All participants underwent measurement of plasma protein C activity and genomic DNA analysis. Using PCR amplification and Sanger sequencing, the study targeted both exon 7 of the PROC gene—where the rare p.Lys193del deletion mutation is located—and three known promoter polymorphisms: −1654 C/T, −1641 G/A, and −1476 T/A.
The results revealed several important findings. First, 7.2% of DVT patients were carriers of the p.Lys193del mutation, a significantly higher frequency than in the control group (0.97%). This indicates a 7-fold increased risk associated with this single mutation. Second, 6.1% of patients were homozygous for the C-G-T haplotype across the three promoter SNPs, compared to only 1% of controls, suggesting a similarly elevated risk. Notably, these two genetic risk factors were found in 11.1% of all DVT cases, yet many of these individuals showed normal or near-normal protein C activity in functional assays, indicating that standard laboratory testing could miss these inherited thrombophilic conditions.
The authors argue that these findings highlight a distinct genetic profile for thrombophilia in the Chinese population, and that current diagnostic strategies—largely modeled after Western data—may overlook meaningful risk in East Asian patients. As a result, they propose incorporating targeted PROC gene sequencing into standard thrombophilia panels in China and similar populations, particularly for patients with unexplained or recurrent DVT. This approach would support more accurate risk stratification, better individualized anticoagulation therapy, and ultimately improved patient outcomes.
In conclusion, this study underscores the importance of population-specific research in precision medicine, revealing genetic markers with significant clinical implications for the diagnosis and management of DVT in East Asia. It advocates for a shift in diagnostic strategy from sole reliance on protein activity assays to the inclusion of molecular genetic screening in appropriate patient populations.