A common haplotype of the annexin A5 (ANXA5) gene promoter is associated with recurrent pregnancy loss

作者：Bogdanova Nadia; Horst Juergen; Chlystun Marcin; Croucher Peter J P; Nebel Almut; Bohring Axel; Todorova Albena; Schreiber Stefan; Gerke Volker; Krawczak Michael; Markoff Arseni^*

来源：Human Molecular Genetics, 2007, 16(5): 573-578.

DOI：10.1093/hmg/ddm017

We sought to verify whether variation in the promoter of the gene encoding placental anticoagulant protein annexin A5 (ANXA5) represents a risk factor for recurrent pregnancy loss (RPL). Sequence analysis of 70 German RPL patients, all known to carry neither factor V Leiden nor a prothrombin mutation, revealed four consecutive nucleotide substitutions in the ANXA5 promoter, which were transmitted as a joint haplotype (M2). Reporter gene assays revealed that M2 reduces the in vitro activity of the ANXA5 promoter to 37-42% of the normal level. The possible relationship between M2 and RPL was evaluated by comparing RPL patients with two independent control groups recruited from the registry of the Institut fur Humangenetik in Munster and the PopGen biobank in Kiel, respectively. Carriers of M2 were found to exhibit a > 2-fold higher RPL risk than non-carriers (odds ratio, 2.42; 95% confidence interval, 1.27-4.58) when using unselected controls (PopGen) and an almost 4-fold higher risk when using the Munster 'super-controls', i.e. women with successful pregnancies and no previous history of pregnancy losses (odds ratio, 3.88; 95% confidence interval, 1.98-7.54). This statistically significant association should facilitate the development of improved prognostic algorithms for RPL, involving a more precise assessment of individual disease risks, and provide a guide to offering adequate therapies where relevant.

• 出版日期2007-3-1
• 单位河北医科大学