Alpha 2-macroglobulin 5 bp insertion/deletion polymorphism increases the risk of recurrent venous thromboembolism

Ahmad, AbrarLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,Skåne University Hospital (author)

Alpha 2-macroglobulin (A2M) is a protease inhibitor that has been reported to neutralize thrombin, which may decrease the risk of thrombosis. A 5-base pairs (bp) insertion/deletion polymorphism (rs3832852) at the splice acceptor site of exon 18 has been shown to affect the binding of A2M with proteases. However, the role of this important variant in A2M in recurrent VTE is unknown. We investigated the role of 5 bp insertion/deletion polymorphism in VTE recurrence in a follow up study. A2M 5 bp insertion/deletion polymorphism was genotyped in Malmö Thrombophilia Study (MATS, n = 1465, with follow up of ~10 years) by TaqMan Allelic Discrimination assay. Univariate Cox regression analysis showed that A2M polymorphism was significantly associated with higher risk of VTE recurrence (hazard ratio [HR] = 2.61, 95% confidence interval [CI] = 1.06–6.45, P = 0.037). This association remained significant (HR = 2.61, 95% CI = 1.06–6.47, P = 0.038) even after adjusting for sex, family history of VTE, thrombophilia and acquired risk factors for VTE. In conclusion, our results indicate that patients with A2M 5 bp insertion/deletion polymorphism are at significantly higher risk of VTE recurrence and this may predict VTE recurrence.

Sundquist, KristinaLund University,Lunds universitet,Allmänmedicin, kardiovaskulär epidemiologi och levnadsvanor,Forskargrupper vid Lunds universitet,Family Medicine, Cardiovascular Epidemiology and Lifestyle,Lund University Research Groups,Shimane University,Icahn School of Medicine at Mount Sinai(Swepub:lu)med-ksq (author)
Svensson, Peter J.Skåne University Hospital(Swepub:lu)medf-psv (author)
Sundquist, JanLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,Icahn School of Medicine at Mount Sinai,Shimane University,Skåne University Hospital(Swepub:lu)med-jsu (author)
Zöller, BengtLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-bzo (author)
Memon, Ashfaque A.Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-aqm (author)
Allmänmedicin och klinisk epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

By the author/editor: Ahmad, Abrar; Sundquist, Krist ...; Svensson, Peter ...; Sundquist, Jan; Zöller, Bengt; Memon, Ashfaque ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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