Anticoagulant protein C p.Lys193del mutation and promoter region polymorphisms: Genetic risk factors of deep venous thrombosis

Objective: Deep venous thrombosis (DVT), a potentially life-threatening condition with a high clinical incidence, represents a significant healthcare burden in China. This study aims to investigate the prevalence of protein C (PROC) p.Lys193del mutation and promoter polymorphisms in patients with DVT in Shanghai, China.
Methods: A total of 180 patients diagnosed with DVT and 103 healthy controls underwent polymerase chain reaction amplification targeting two specific regions of the PROC gene for genetic analysis of the p.Lys193del mutation and promoter polymorphisms.
Results: The p.Lys193del mutation was significantly more prevalent in the DVT group, with 13 carriers identified (7.2%, 13/180), compared to only one carrier in the control group (0.97%, 1/103; P<0.05). Genetic analysis of PROC promoter polymorphisms revealed distinct allele distribution patterns between the groups, with significantly different frequencies for the -1654 C,-1641 G and -1476 T alleles in DVT group versus control group (P<0.05). Corresponding genotype analysis showed significant intergroup differences in the three homozygous variants: -1654C/C, -1641G/G and -1476T/T, all of which exhibited significantly higher frequencies in the DVT group compared to control group (11.1% vs. 1.9%, P<0.01).
Conclusions: The PROC p.Lys193del mutation, an established genetic risk factor for DVT, accounts for about 7.2% of DVT cases. Furthermore, three promoter polymorphisms (-1654C/C, -1641G/G, -1476T/T) were present as homozygous genotypes in 6.1% (11/180) of DVT group, demonstrating statistically significant association with thrombotic risk compared to healthy controls (P<0.05). These findings position both the p.Lys193del mutation and the promoter haplotype variants as independent genetic risk factors for venous thromboembolism in the studied population.