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Hematological disorders like Aplastic anemia are quite frequent in Pakistan. Human leukocyte antigen (HLA) system, have been implicated in the development of Aplastic anemia in various population-based studies, The aim of this study was to determine the role of the HLA Class I and Class II alleles in genetic susceptibility to Aplastic anemia in Pakistani patients. HLA A*, B* and DRB1* alleles were analyzed, in 61 Pakistani patients (Females n = 22, Males n = 39) and the control group consisted of 200 ethnically matched individuals (Females n = 89, Males n = 111). The allele frequency of DRB1*15 was found significantly higher in patients 0.36 (p = 0.001 with odds ratio = 1.97), as compared to the controls 0.212. Although DRB1*03 percent frequency was significantly higher in controls 0.175 (p = 0.023) with odds ratio = 0.514, as compared to patients 0.106.Therefore DRB1*15 emerged as a susceptible allele and DRB1*03 as a protective allele in Pakistani Aplastic anemia patients and control samples. No significant difference was found in allele frequencies of other HLA class I and HLA class II alleles for both patients and controls. Three haplotypes A*02 B*40 DRB1*15 (p = 0.021), A*31 B*51 DRB1*13 (p = 0.12) and A*33 B*58 DRB1*15 (p = 0.000) showed significant variations in the two groups.

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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.