Functional Polymorphisms In The Promoter Regions Of The Fas And Fas Ligand Genes In Women With Preeclampsia

Objective: To estimate whether Fas and FasL polymorphisms in thepromoter regions can alter the transcriptional activities and thus alter riskof preeclampsia.Methods: By means of polymerase Chain Reaction and RestrictionFragment Length Polymorphism, A-670G polymorphism at position-670,G-1377A polymorphism at position -1377 in the Fas gene andC-844T polymorphism at position -844 in the FasL gene were detected in140 women with preeclampsia (75 with mild preeclampsia and 65 withsevere preeclampsia) and 170 normotensive control women withuncomplicated pregnancy. Investigators were blinded to clinicaloutcomes.Results: The Fas-670 G Allele frequency in preeclampsia group weresignificantly higher than those in control group(56.4% vs 36.2%)(P<0.001). The Fas -1377 A Allele frequency in preeclampsia group werealso significantly higher than those in control group(62.9% vs 42.9%)(P <0.001) . However, the FasL-844 C/T polymorphism was notassociated with an increased risk of preeclampsia. Consistently, the Fashaplotype genotypes with 2-4 variant (risk) alleles (-670G and -1377A) were associated with an increased risk of preeclampsia compared to 0-1 variants (adjusted OR=5.27, 95% CI=2.53～10.97). Furthermore, when we evaluated these three polymorphisms together, we found that the combined genotypes with 4-6 variant (risk) alleles (-670G, -1377A,and -844C) were associated with an increased risk of preeclampsia compared to 0-3 variants(P<0.001). In addition, The Fas-670 G Allele frequency in severe preeclampsia group were significantly higher than those in mild preeclampsia group (64.6% vs 49.3%)( P=0.010).Conclusion: The G Allele of Fas-670 gene and the A Allele of Fas-1377 gene might be risk genetic markers of preeclampsia. In patients with preeclampsia, there is the association between G Allele of Fas-670 gene and severity of preeclampsia. Fas and FasL polymorphisms appear to jointly contribute to risk of preeclampsia.