Browsing by Author "Mukasa Kafeero, Hussein"

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Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management
(Hindawi, 2022-01-11) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Kato, Charles Drago; Wampande, Eddie; Kajumbula, Henry; Kateete, David; Walusansa, Abdul; Kudamba, Ali; Kigozi, Edgar; Katabazi, Fred Ashaba; Namaganda, Maria Magdalene; Ssenku, Jamilu E.; Sendagire, Hakim
Background. Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. Methods. A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson’s chi-square, multinomial logistic regression, and Mann–Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0:05 was considered statistically significant. Results. Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0:05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0:05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0:05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0:05). Conclusion. There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.
Tumor Necrosis Factor-α-863C/A and 1031 T/C Single nucleotide polymorphic sites (SNPs) may be putative markers of HBV disease prognosis among Caucasoids: Evidence from a systematic review with meta-analysis
(Elsevier, 2022-01-19) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Walusansa, Abdul; Sendagire, Hakim
Background: The pathogenesis and prognosis of hepatitis B virus (HBV) infection have been correlated with genetic polymorphisms in the gene loci within the promoter region of the immune system modulator molecules such as the cytokines including the tumor necrosis factor (TNF)-alpha. Besides, these polymorphisms vary at population levels but it is not conclusive whether races are involved or not. We aimed at testing the hypothesis that the SNPs in the promoter region of the TNF-alpha gene may have different effects in the Caucasoid populations by pooling the odds of association with the clearance/increased risk of the HBV infection from a large sample size obtained from many primary studies. We searched Scopus, PubMed, EMBASE, Cochrane, Willy and Google scholar databases for the published studies between January 1998 to December 2020. Studies that investigated the association between the TNF-α-238G/A, -308G/A, -857C/T, -863C/A and -1031 T/C gene promoter polymorphisms with the resolution/increased risk of HBV infection published in English and in peer reviewed journals were included. The odds ratios were used to evaluate the association of the TNF-α-gene SNPs with the risk/resolution of the disease. This study is registered on PROSPERO, number CRD42021266944. Results: A significant association was observed between the TNF-α-857 homozygous mutation TT and its allele T with reduced risk of infection or resolution of the disease among both the Caucasoids and the Mongoloids (p < 0.05, OR < 1.0). In contrast, the TNF-α-1031 wild type genotypes TT; p = 0.001, OR = 0.634, 95%CI = [0.489 to 0.822%] and its allele T; p = 0.001, OR = 0.701, 95%CI = [0.571 to 0.860%] were significantly associated with reduced risk of infection or increased chances of resolution of the disease among the Caucasoids only. However, the TNF-α-863 homozygous mutation AA or its allele A and the TNF-α-1031 heterozygous mutation CT or the allele C were significantly associated with unresolved HBV infection among the Caucasoids (p < 0.05, OR > 1.0) but not among the Mongoloids. Conclusion: Tumor Necrosis Factor-α-863C/A and 1031 T/C polymorphic sites may be putative markers of HBV disease prognosis and pathogenesis among the Caucasoid populations but not among the Mongoloid populations. Future research therefore should focus on the role of these presumed TNF-α-polymorphisms in the clinical profile of the HBV infections targeting an African or Negroid population.