Impact of ABO blood groups on residual pulmonary vascular obstruction in patients with unprovoked pulmonary embolism

After completing anticoagulant therapy for acute pulmonary embolism (PE), patients may have persistent thrombotic materials in the lung, causing residual pulmonary vascular obstruction (RPVO). Detectable by imaging, RPVO is associated with an increased risk of recurrent events and chronic complications. Little is known about RPVO risk factors including genetics. ABO is known to be associated with RPVO-related traits, such as recurrent PE, chronic thromboembolic pulmonary hypertension. This study specifically investigates the association between genetically determined ABO blood groups and RPVO in patients with unprovoked-PE. This work relies on two French cohorts of patients with unprovoked-PE, EDITH and PADIS-PE, and a Canadian one, REVERSE-I, with RPVO measurements. In each study, five ABO polymorphisms were used to infer ABO blood groups: rs8176719-delG, rs41302905-T, rs2519093-T, rs1053878-A and rs8176743-T alleles tagging for O1, O2, A1, A2 and B, respectively. Associations between ABO blood groups and RPVO were assessed in each study using a Compound Poisson Gamma model, which accounts for the semi-continuous RPVO distribution. Study-specific results were then combined through meta-analysis. The meta-analysis included 586 patients with unprovoked-PE, providing sufficient power (>80%), as confirmed by simulations, to detect moderate genetic effects (1.3-fold increased risk) of common variants (allele frequency ≥0.05). Despite this, no significant association was observed between ABO blood groups and RPVO. ABO blood groups are unlikely to be major risk factors for RPVO. Nevertheless, this study provides an important foundation for future large-scale genetic investigations aimed at identifying the molecular determinants of RPVO. NCT00740883