Early pregnancy loss in celiac women: The role of genetic markers of thrombophilia

Abstract Background Adverse pregnancy outcomes are more frequent in celiac than in non-celiac women. Aims To investigate a possible role of genetic prothrombotic variants in early pregnancy loss of celiac women. Methods Thirty-nine celiac women who had experienced early pregnancy losses (at least two losses within the first 3 months of pregnancy), and 72 celiac women with a history of one or more normal pregnancies and no pregnancy loss (controls) entered the study, at the moment of diagnosis for celiac disease. A clinical history was obtained from each woman. DNA from leukocytes was tested for: factor V Leiden (mutation G1691A), factor V R2 (H1299R), factor II (G20210A), methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), beta-fibrinogen (−455 G>A), PAI-1 alleles 4G/5G, factor XIII (V34L), and HPA-1 (L33P). Results Age at diagnosis was significantly higher ( p  = 0.002) in the celiac women with pregnancy losses than in controls. Of the gene variants studied, the allelic frequency of 4G variant of PAI-1, and the frequency of mutant genotypes were significantly more frequent in the group of celiac women with early pregnancy loss ( p  = 0.00003 and 0.028, respectively). Surprisingly, the beta-fibrinogen −455 G>A genotype distribution (but not the allelic frequency of the variant allele) significantly differed between the two groups, since variant genotypes were more frequent in the control group ( p  = 0.009). Conclusion The 4G variant of the PAI-I gene may predispose to miscarriage a subset of celiac women; these data should be verified on larger populations.