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Fas –FasL genotype and phenotype in preeclampsia

Karen P. Pendeloski1, Thalita F. Lobo1, Maria R. Torloni1, Rosiane Mattar1 and SILVIA DAHER1*
  • 1 Sao Paulo Federal University, Obstetrics, Brazil

Pre-eclampsia (PE), a hypertensive disorder specific to pregnancy, is one of the major causes of maternal and fetal morbidity and mortality. Impaired apoptosis or programmed cell death inhibiting trophoblastic invasion seems to be involved in the development of preeclampsia. The FAS/FASL system, one of the most important inducers of apoptosis, is usually expressed in placental tissue throughout gestation. Single-nucleotide polymorphisms (SNP) have been identified in the FAS-FASL gene promoters. A polymorphism at the -670 position (rs1800682) in the FAS gene leads to decreased FAS production, while a polymorphism at the -844 position (rs763110) of the FASL gene leads to increased expression of this molecule. SNPs of FAS and FASL genes and impaired synthesis of these molecules have been associated with different diseases. Other investigators have reported abnormal expression of FAS and FASL molecules in placental tissue of preeclamptic patients. However, the role of the FAS/FASL apoptosis pathway in the pathogenesis of PE is still not completely clear. Therefore, our aim was to investigate a possible association between FAS (-670) and FASL (-844) gene polymorphisms and messenger RNA (mRNA) expression in Brazilian women with PE. This case-control study included 130 preeclamptic patients and 260 controls. PE was defined as hypertension after 20 weeks gestation (systolic pressure ≥ 140mm or diastolic ≥ 90mm Hg) in a previously normotensive woman, accompanied by proteinuria (urinary excretion of ≥ 0.3 g protein in a 24-hour specimen). The control group included normotensive pregnant in the index pregnancy with a history of at least two previous normal pregnancies, without any maternal or fetal disorders. Genomic DNA was extracted by the DTAB/CTAB method from whole blood. FAS (rs1800682) and FASL (rs763110) gene polymorphisms were genotyped by the restriction fragment-length polymorphism (RFLP) method. Briefly, PCR products were digested with the following restriction endonucleases: BstNI and BsrDI, respectively. Total RNA was extracted using the TRIzol reagent from isolated PBMCs. RNA expression levels of the 2 target genes (FAS and FAS-L) and 2 housekeeping genes (GAPDH and ACTB) were analyzed by Real-Time PCR. TaqMan Gene Expression Assays were used for the target genes FAS (Hs00907759_m1) and FASL (Hs00181225_m1) and the endogenous controls GAPDH (Hs99999903_m1) and ACTB (Hs99999905_m1). Chi-squared and Fisher’s exact tests were used to analyze categorical and continuous variables, respectively. All quantitative PCR data were analyzed using the relative expression software tool REST 2009 (Relative Expression Software Tool). p<0.05 was considered significant. The study was approved by the university´s ethics committee, and informed consent was obtained from the participants. All SNPs in PE and control groups were in Hardy-Weinberg equilibrium. The genotype frequencies for the FAS polymorphism were 19.8% AA, 45.2% AG and 34.9% GG in the PE group; and 25.3% AA, 50.2% AG and 24.5% GG in controls (p=0.09). Genotypic frequencies of FASL were 23.8% TT, 42.3% TC and 33.8% CC in the PE group; and 33.5% TT, 46.5% TC and 20% CC in controls (p=0.007). Patients with PE and controls presented similar FAS gene mRNA expression (P(H1)=0.514; hypothesis test). FASL mRNA was upregulated in patients with PE compared to control group (P(H1) = 0.007; hypothesis test). In conclusion, this study suggests an association between FASL (-844) gene polymorphisms and PE and that these women also have impaired FAS/FASL systems due to abnormal FASL expression.

Acknowledgements

This work was supported by CAPES, CNPq (307337/2012-0) and FAPESP (2009/54729-6).

References

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Keywords: Preeclampsia, gene polymorphism, Apoptosis, Fas-FasL, trophoblast invasion

Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.

Presentation Type: Oral Presentation

Topic: Immunology of reproduction

Citation: Pendeloski KP, Lobo TF, Torloni MR, Mattar R and DAHER S (2015). Fas –FasL genotype and phenotype in preeclampsia. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00337

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Received: 29 May 2015; Published Online: 15 Sep 2015.

* Correspondence: Prof. SILVIA DAHER, Sao Paulo Federal University, Obstetrics, São Paulo, São Paulo, 01415002, Brazil, silviadaher@hotmail.com