The results of our analysis of Fas alleles Fas
The results of our analysis of Fas alleles, Fas 670 A>G, FasL alleles, and FasL IVS2nt 124 A>G for cases and controls are shown in Table 2. For Fas 670, we found statistically significant differences between the two groups regarding the AA Xylometazoline HCl (P=0.040) and GG/AG (P=0.040) as well as the A and G allele frequency (P=0.047 for both), while no statistically significant differences were found regarding AG or GG genotypes (P=0.421, 0.307 respectively; Table 2). For FasL, there were no significant differences between the cases and controls regarding allele or genotype frequencies.
Table 3 shows the results for allele frequencies comparing severe preeclamptics with mild preeclamptic cases. No significant differences were found.
No significant correlation was found between patients’ genotypes and fetal complications. We did not find any statistically significant correlation between Fas 670 gene polymorphism and intrauterine growth retardation (r=0.091, P=0.082), intrauterine fetal death (r=0.087, P=0.072), and prematurity (r=0.075, P=0.061). Also, we did not find any statistically significant correlation between FasL gene polymorphism and intrauterine growth retardation (r=0.085, P=0.071), intrauterine fetal death (r=0.073, P=0.062), and prematurity (r=0.086, P=0.074).
Table 4 summarizes our findings using a multiple logistic regression model for analyzing the simultaneous effect of the polymorphisms studied on the risk of preeclampsia. After adjusting for age and parity, we found that the presence of the Fas gene polymorphism was associated with an increased risk of preeclampsia (OR=3.8, CI=2.1–10.4), while the presence of the FasL IVS2nt 124 A>G gene polymorphism was associated with a decreased risk of preeclampsia (OR=0.328, CI=0.122–0.469).
Discussion Our findings confirm an association of the Fas 670 A>G gene polymorphism with pre-eclampsia in that we found the GG/AG genotype in 84% of women with pre-eclampsia versus 60% of normal women. Moreover, the AA genotype was found in 36% of normotensive women and only 16% of preeclamptic women. Finally, the G allele frequency was higher in the preeclamptic group. Logistic regression analysis showed that the Fas A670G polymorphism could be considered an independent risk factor for preeclampsia and is associated with an increased risk of nearly 4-fold. Our analysis also suggests that the presence of the FasL IVS2nt 124 A>G gene polymorphism is associated with a decreased risk of preeclampsia. Our data are consistent with those of Ciarmela (2010); who observed the Fas 670 G gene variant in 42 Italian pre-eclamptic patients (84%) versus 96 members of the general population control group (67.6%; P=0.029). They also noted the Fas 670 AA genotype in 33 normotensive pregnant women (37.1%) compared with only 5 out of 31 preeclamptic pregnant women (16.1%). Both our results and those of Ciarmela et al. contrast with the findings of Sziller et al. (2005); who found 82% of Hungarian pre-eclamptics with GG/AG and 62.9% of controls with GG/AG and that the carriage rate of the Fas 670 G allele variant was higher among preeclamptics (59.7%) than among controls (42.1%; P=0.01). Hu et al. (2005) and Polavarapu et al. (2013) found no differences in the Fas or Fas ligand genotype/allele frequency between preeclamptic and normotensive placentas. We speculate that the populations studied by these investigators might be genetically distinct from ours. Sziller et al., 2005; noted that the Fas 670 G allele increases the risk of preeclampsia and preeclampsia-associated IUGR in women who deliver at <37 weeks. We did not find the latter, although this could be due to our small sample size. We recognize that our study has limitations. Among these is our relatively small sample size. On post hoc analysis, we found that our study was powered to detect a minimal difference of 20% between groups (alpha=0.05 and power=80%). In successful pregnancies, binding of trophoblast-associated FasL to Fas-expressing activated maternal T lymphocytes that invade the trophoblast during implantation induces apoptosis in Fas-bearing maternal T cells, allowing fetal trophoblast to invade the myometrium while escaping immune recognition (Abrahams et al., 2004). The Fas-expressing invading trophoblasts may also undergo apoptosis from FasL-expressing maternal T cells, limiting the extent of myometrial invasion (Frangsmyr et al., 2005). The disturbed Fas-mediated apoptosis resulting from genetic polymorphism could be involved in the pathogenesis of preeclampsia and HELLP syndrome (Miko et al., 2009).