Association of ADAMDECI haplotype with high factor VIII levels in venous thromboembolism

作者：Berger Mario; Moscatelli Henriette; Kulle Bettina; Luxembourg Beate; Blouin Katja; Spannagl Michael; Lindhoff Lase Edelgard; Schambeck Christian M^*

来源：Thrombosis and Haemostasis, 2008, 99(5): 905-908.

DOI：10.1160/THOB-01-0059

• factor VIII
• inherited thrombophilia
• metalloprotease
• venous thromboembolism

A suggestive locus sociated with familial high factor VIII (FVIII) levels in venous thromboembolism. The ADAMDEC I gene is a candidate expressing an ectodomain sheddase. However, the ectodomain of the clearance receptor for FVIII, the low-density lipoprotein receptor-related protein (LRP), is subject to proteolysis by metal-loproteases like ADAMDEC 1. Other LRP-interacting proteins are lipoprotein lipase (LPL) and t-PA. For an association study, 165 thrombotic patients with high FVIII levels (from the MAIS-THRO, i.e. Main-Isar-thrombosis register) were included. All patients with known causes for high FVIII levels had been previously excluded. The patients were compared with 214 healthy blood donors. Polymorphisms with usually a minor allele frephisms of LPL gene, eight SNPs of the t-PA gene, and five SNPs of the ADAMDEC I gene, were analyzed. Haplotype differences were calculated using PHASE. A new polymorphism in intron 7 of the the t-PA gene with a minor allele frequency of 2.2% was indentified. not show any significant association between genotype and disease status. Interestingly, the ADAMDECI haplotype (rsl2674766, rs 10087305, rs2291577, rs2291578, rs3765124) differed between cases and controls (p=0.04). In particular, the TGTGG haplotype showed a difference. In conclusion, the ADAMDEC I haplotype may indicate an underlying mechanism for high FVIII levels. The only moderate linkage disequilibrium may be due to a possible causal polymorphism in distant introns or the promoter region against a polygenic background.

• 出版日期2008-5