Abstract
BACKGROUND: Venous thromboembolism (VTE) is a significant global health concern, with an annual incidence of approximately 1-2 per 1000 individuals. VTE is a major cause of morbidity and mortality worldwide, leading to substantial healthcare costs due to hospitalizations, long-term anticoagulation therapy, recurrent thrombotic events and the need for lifelong clinical management. The burden of VTE is particularly pronounced in aging populations, with incidence rates increasing exponentially after the age of 50. Despite its significant impact, the genetic underpinnings of VTE remain incompletely understood. This study investigates the association of Lp(a) gene polymorphisms (93C > T and 121G > A) and Lp(a) expression with VTE risk. METHODS: A case-control study was conducted, enrolling 101 VTE cases and 110 healthy, age- and gender-matched controls. Genotyping was performed using PCR-RFLP, and serum Lp(a) levels were quantified using ELISA. Genotype distribution and their association with VTE risk was determined by statistical analyses. RESULTS: The +121 G > A polymorphism exhibited a significant protective effect, with the GA genotype more prevalent in controls than cases (OR = 0.41, 95 % CI = 0.23-0.73, p = 0.002). Additionally, the combined GA + AA genotypes were significantly associated with a lower VTE risk (OR = 0.44, p = 0.003). Serum Lp(a) levels were elevated in VTE cases (mean VTE 36.41 mg/dl) compared to controls (mean 32.00 mg/dl, p < 0.84). Notably, this difference was most pronounced in the 30-70 mg/dl subgroup (p < 0.01). D-Dimer was significantly elevated in VTE (p < 0.001) and GA + AA genotype was significantly more frequent in control subjects with D-Dimer levels <500 ng/ml (OR = 0.23, 95 % CI = 0.05-0.95, p = 0.04. LP (a)+121 G > A variant genotype was significantly higher in controls for males, smokers and BMI ≤25 than VTE cases (p < 0.05). No significant difference was found in LP(a) +93C > T with VTE risk. CONCLUSION: Our study concludes the inverse role of Lp(a) polymorphic variation +121 G > A in the pathogenesis of VTE. +93C > T variant and serum lipoprotein (a) levels did not increase the risk of pathogenesis of VTE. However, gender specific impact of LP(a) on VTE is plausible.