1102 The haplotype M 2 within the ANXA 5 gene is independently associated with the occurrence of deep venous thrombosis

Dear Sir, Despite increased awareness of the risk factors (1, 2) of venous thromboembolism (VTE), it remains the third most common cardiovascular affliction after ischaemic heart disease and stroke (3, 4). Annexin V (ANXA5), the most abundant member in the family of annexins, is found in many tissues and in the bloodstream, and plays a potent antithrombotic role (5). A common haplotype (M2) within the ANXA5 gene has been demonstrated to diminish the ANXA5 promoter activity and to be a risk factor for obstetric complications (6, 7). In a cohort of patients with documented deep venous thrombosis (DVT) occurred in a leg, we investigated whether the presence of the M2 haplotype is associated with the occurrence of VTE. Between January 2004 and December 2008, we investigated 231 not anticoagulated patients (median age: 46 years; range: 17–82), 98 men and 133 women, with a documented episode of DVT in a leg, who were referred at least three months after the thrombotic episode for a work-up to the Thrombosis Centre at the IRCCS „Casa Sollievo della Sofferenza“, San Giovanni Rotondo (FG), Italy. The median age (range) at the time of the first thrombotic episode was 39 years (18–78). A complete clinical summary with emphasis on personal and family history for thromboembolic disease was obtained; pulmonary embolism (PE) was diagnosed by helical computed tomography (CT), angiography, or high probability ventilation-perfusion lung scan, as required during the routine diagnostic work-up. DVT were defined as idiopathic when none of the circumstantial vascular risk factors (surgery, immobilisation, pregnancy, trauma) was recorded. All others were classified as provoked. Patients with malignancy or varicose veins were not included. Overall, 36 (15.6%) individuals (19 men, 17 women) also experienced an objectively confirmed episode of PE. A recurrence of DVT was observed in 43 (18.6%, 95% confidence interval (CI): 14.1–24.2) individuals (21 men and 22 women). A reported recurrent VTE was accepted as such if it had been confirmed by objective diagnostic testing, i.e. ultrasonography showing a newly non-compressible venous segment or perfusion lung scan revealing defects in previously perfused areas or in the original area if the initial episode was previously demonstrated to be resolved in case of PE. Three hundred-eighty two apparently healthy subjects (187 men and 195 women; median age 34 years, range 18–66) randomly selected from a Southern Italian general population without a history of VTE served as controls. Both cases and controls were Caucasian and from the same region. The two groups were comparable for sex and social status. After approval of the local Ethics Committee, the study was carried out according to the Principles of the Declaration of Helsinki; informed consent was obtained from all the subjects. Correspondence to: Elvira Grandone, MD Unita' di Aterosclerosi e Trombosi I.R. C.C. S. „Casa Sollievo della Sofferenza“ S. Giovanni Rotondo (FG), Italy Tel. : +39 0882 416273, Fax: +39 0882 416273 E-mail: e.grandone@operapadrepio.it