Single-Nucleotide Polymorphisms of FAS and FASL Genes and Risk of Idiopathic Aplastic Anemia

Abstract

FAS/FASL signaling system plays a vital role in the regulation of apoptosis, envisaged as a death process required for immune surveillance to prevent autoimmunity and tumorigenesis along with several other biological activities. Several single-nucleotide polymorphisms (SNPs) of FAS/FASL system can result in aberrant apoptosis, which can cause different cancers and autoimmune diseases. Aplastic anemia (AA) is an autoimmune dysfunction characterized by peripheral blood pancytopenia associated with hypoplasia of bone marrow. The aim of this study was to screen Pakistani AA patients and controls for two Fas SNPs rs2234767 and rs1800682 and two FASLG SNPs rs763110 and rs5030772. Genotyping of 392 DNA samples was done by Tetra-ARMS polymerase chain reaction. Genotypic frequencies of Fas rs1800682 and FASLG rs5030772 showed significance difference in their distribution in both controls and patients, while Fas rs2234767 and FASLG rs763110 SNPs had no such difference. Carriers of rs1800682 AG+GG had a very odd ratio of 4.63, with 95% confidence interval (CI) of 3.01-7.11, while individuals with FASLG rs5030772 AG+GG were more common in controls than patients with OR 0.53 and 95% CI of 0.34-0.83. Cumulative effects of these SNPs were analyzed, and they showed almost similar trends; however, Fas rs2234767 and FASLG rs763110 genotypes in combination with Fas rs1800682 and FASLG rs5030772 demonstrated significant association. This study provided information that endorsed the involvement of FAS/FASL system SNPs in the pathogenesis of AA; further studies should be designed to understand the exact role of SNPs that can help in early diagnosis and treatment.

Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia

“…Case 4 carried both AA-risky and -protective HLA alleles, whereas Case 11 (i.e., the patient suffering a hepatitis-associated AA subtype) only carried AA-protective alleles. For the six patients that underwent whole-exome sequencing of whole blood, we also assessed for the presence of other AA-risky non- HLA SNP, including telomeric repeat binding factor 1 ( TERF1 ) (rs3863242) [ 25 ], CTLA4 (rs231775) [ 26 ], PDCD1 (rs36084323) [ 27 ], IFNG (rs2430561) [ 28 ], FAS (rs1800682) [ 29 ], and FOXP3 (rs3761548) [ 30 ]. The only one that was detected was the CTLA4 p.T17A (rs231775) SNP, with five of the six cases carrying the AG genotype and Case 9 carrying the GG genotype that has been reported as AA-risky in Chinese Han [ 26 ] but not in Caucasians [ 31 ].…”

Epidemiology of aplastic anemia: a study of 1324 cases

“…Other smaller studies on some of these patients have revealed genetic predispositions for AA in FAS/FASL system, GSTM1 and GSTT1 and different HLA alleles [32][33][34]. Similarly, low fraction of PNH positivity may also point toward underlying non-immune mechanisms in the disease pathogenesis.…”

FASandFASLvariations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients

“…9 Because the allele G of FAS c.671A > G was previously associated with lower apoptosis of damaged cells, 13 these results were not expected by us. However, activation of FAS/FASL was described as an important mechanism in erythroid maturation 50 and regulation of red blood cell homeostasis, 51 and Rehman et al 52 observed that G allele of FAS c.-671A > G increased aplastic anemia risk. Moreover, deletion of FAS in lymphocytes caused lymphopenia in mice, 53 suggesting that FAS expression in lymphocytes is required for their survival and/or proliferation.…”

“…G was previously associated with lower apoptosis of damaged cells, 13 these results were not expected by us. However, activation of FAS/FASL was described as an important mechanism in erythroid maturation 50 and regulation of red blood cell homeostasis, 51 and Rehman et al 52 observed that G allele of FAS c.-671A . G increased aplastic anemia risk.…”