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Introduction: The human leukocyte antigen (HLA) region on chromosome 6p21 is well known to carry the most important genetic factors in susceptibility to psoriasis. Different HLA alleles and haplotypes have been reported to be associated with psoriasis in different populations. Psoriasis has a variable age of onset and, based on this, it can be classified into two types; type I with age of onset before 40 years of age and type II with age of onset after 40 years of age. The objective of this study was to determine the association of HLA class I and class II alleles and haplotypes with disease and stratification using age of onset in Pakistani psoriatic patients. Methods: A group of 603 individuals (326 cases and 277 controls) were analyzed for HLA class I and II alleles and haplotype association by sequence specific PCR. The association was further analyzed according to the age of onset of the patients. Results: We found that HLA alleles B*57 and Cw*06:02, DQB1*03:03:02 are strongly associated with early onset psoriasis, while alleles B*15, DRB1*13:02 and DQB1*03:03:02 are associated with late-onset psoriasis. Cw*06:02 allele was not associated with late-onset psoriasis patients. Allele DQB1*03:03:02 had the highest odds ratio in all patients. We found a novel association specifically with late-onset psoriasis samples with the haplotype HLA-A*11; B*15; Cw*04; DRB1*15; DQB1*05 (Pc = 3.60 × 10−7). We also found strong association with previously reported extended haplotype EH-57.1: HLA-B*57; Cw*06:02; DRB1*07:01; DQB1*03:03:02 in all our patients (Pc = 8.34 × 10−07). Conclusion: Our results show that different HLA class I and II alleles and haplotypes are associated with psoriasis at different age of onset. In this study, we have reported novel alleles and haplotype association with late-onset psoriasis. Our data confirm the previous strong associations with HLA alleles and haplotypes and also reports novel alleles and haplotype association in Pakistani psoriasis patients. [ABSTRACT FROM AUTHOR]

Typhoid fever caused by Salmonella enterica serovar Typhi has become a serious public health issue due to the development of resistance worldwide especially in developing countries including Pakistan. The aim of this study was to assess the antimicrobial susceptibility pattern of Salmonella Typhi isolated from human blood samples and detect genes by using PCR technique. Total 400 blood samples of typhoid confirm patients were cultured on Salmonella-Shigella agar to isolate Salmonella Typhi. The bacterium was identified through biochemical tests and susceptibility was checked against ten different antibiotics by using disk diffusion method. PCR technique was used to detect different genes after extraction of DNA using phenol-chloroform method. Salmonella typhi (27%) was isolated from blood samples of typhoid patients. Among these, 41% were resistant to ciprofloxacin followed by 34% of ceftriaxone and 25% of streptomycin. Isolated strains were positive for the presence of gyrase A, CMY-2, spvC and InvA genes detected through PCR using specific primers. This study concluded that Salmonella typhi is developing resistance to antimicrobial agents due to the transfer of virulence and resistant genes which may lead to the failure in treatment of typhoid patients in Pakistan. [ABSTRACT FROM AUTHOR]

Objective:: To understand the role of three single nucleotide polymorphisms (SNP) of vitamin D receptor (VDR) gene rs7975232, rs731236 and rs2228570 in Pakistani vitiligo patients and ethnically matched controls. Methods: 196 vitiligo patients and 262 controls were included in this study. Genomic DNA was extracted and polymerase chain reaction, restriction length polymorphism (PCR-RFLP) was done. Results: Genotype CA (rs7975232) was found to be associated with susceptibility (Odd ratio=1.46, 95% CI=1.01-2.13, p=0.046) and TT genotype (rs731236) with protection (Odd ratio=0.48, 95% CI=0.25-0.92, p=0.003) to vitiligo. TT genotype for rs731236 was significantly high in controls and absent in undetermined/unclassified group of patients. Vitiligo patients and controls were also compared on the basis of gender. Genotype CA (OR=2.12, 95% CI=1.18-3.79, p=0.013) and CC (OR =0.21 95% CI=0.06-0.73, p=0.007) for rs7975232 were significantly high in male patients and controls, respectively. For rs2228570 CC genotype was significantly high in controls (OR=0.52, 95% CI=0.2-0.97), p=0.04) while TC genotype showed significant difference between patient and controls (OR=1.93, 95% CI=1.02-3.6), p=0.05). In combined effect haplotype A-T-C was found significantly high in controls as compared with the patients (Odd ratio=0.57, 95% CI=0.34-0.97, p=0.04). Conclusion: VDR polymorphisms may be involved in etiology of vitiligo and future studies should be design to screen large sample size for more VDR polymorphism to get more precise picture. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]