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Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population.

ABSTRACT: BACKGROUND:Human immunodeficiency virus (HIV) infection is a global health burden which ultimately results in acquired immune deficiency syndrome (AIDS). There are multiple host factors which are capable of limiting HIV-1 replication. One of the most important host factors which inhibit HIV-1 DNA synthesis is the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide- like 3G (APOBEC3G). Any genetic variation of this important host factor may influence the host susceptibility to viral infection. OBJECTIVE:The aim of the current study was to evaluate any correlation of APOBEC3G genetic variation rs8177832 with HIV-1 infection. METHODS:The study involved 142 healthy control and 100 HIV-1 infected subjects. The genetic variation rs8177832 of all studied subjects was determined by allele-specific polymerase chain reaction (AS-PCR). RESULTS:The results showed that the distribution of rs8177832 genotypes AA, AG and GG in healthy subjects and HIV-1 subjects was; 42.253%, 42.957%, 14.788% and 66%, 27%, 7% respectively. Statistical analyses of data showed that there was a significant variation in rs8177832 genotype AA in healthy control and HIV-1 infected subjects (42.257% vs 66%; p-value<0.001). CONCLUSION:Thus it was concluded that APOBEC3G rs8177832 AA genotype contributes in genetic predisposition to HIV-1 infection in Pakistani population.

SUBMITTER: Iqbal K

PROVIDER: S-EPMC6416456 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population.

Iqbal Khurshid K Imran Muhammad M Ullah Shafi S Jamal Muhsin M Waheed Yasir Y

Current HIV research 20180101 4

<h4>Background</h4>Human immunodeficiency virus (HIV) infection is a global health burden which ultimately results in acquired immune deficiency syndrome (AIDS). There are multiple host factors which are capable of limiting HIV-1 replication. One of the most important host factors which inhibit HIV-1 DNA synthesis is the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide- like 3G (APOBEC3G). Any genetic variation of this important host factor may influence the host susceptibility to vir ...[more]

PMID: 30338740

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Project description:PurposeApolipoprotein B mRNA-Editing Catalytic Polypeptide-like (APOBEC) enzymes are mutagenic factors contributing to tumor progression and therapy resistance. However, the effects of APOBEC-induced protein changes have not been systematically assessed. Here, we describe the effects of APOBEC on the coding sequence in primary and metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC).MethodsWe determined the enrichment of amino acid (AA) changes resulting from APOBEC mutagenesis in 323 primary BC tumors and 424 metastatic breast cancer (mBC) lesions via comparison with a simulated mutational genomic landscape not under selection pressure. We subsequently explored genes with recurrent APOBEC-associated AA changes and investigated the clonality of individual APOBEC-associated mutations. Using public sequencing data from an independent primary BC and mBC cohort, we further confirm our findings by reporting genes having these enriched AA changes in an APOBEC context.ResultsOur analysis demonstrated that several APOBEC-derived AA changes are significantly enriched compared with a simulated AA change distribution drawn at random. Among the enriched AA changes, Glutamate(E)>Lysine(K) and Glutamate(E)>Glutamine(Q) were mostly found at hotspots in oncogenes, whereas termination codons (Glutamine[Q]>STOP[X] and Serine[S]>STOP[X]) occurred in tumor suppressor genes and, mostly, not at hotspot locations. These mutations are found in genes contributing to BC initiation, eg, introduction of termination codons in TP53, MAP3K1, and CDH1 (in lobular BC) and two oncogenic hotspots in PIK3CA (p.E542K and p.E545K). In endocrine-resistant BC, we observed APOBEC-induced termination codons at ER-modulating genes, KMT2C, ARID1A, NF1, and ZFHX3. Finally, in mBC, compared with single PIK3CA mutations, dual PIK3CA mutations occurred more frequently in an APOBEC context (Fisher's exact P < .001).ConclusionOur results show that APOBEC mutagenesis recurrently targets various known drivers of BC initiation, progression, and endocrine resistance.

Project description:Transcript dosage imbalance may influence the transcriptome. To gain insight into the role of altered gene expression in hereditary colorectal polyposis predisposition, in the present study we analyzed absolute and allele-specific expression (ASE) of adenomatous polyposis coli (APC) and mutY Homolog (MUTYH) genes.We analyzed DNA and RNA extracted from peripheral blood mononuclear cells (PBMC) of 49 familial polyposis patients and 42 healthy blood donors selected according similar gender and age. Patients were studied for germline alterations in both genes using dHPLC, MLPA and automated sequencing. APC and MUTYH mRNA expression levels were investigated by quantitative Real-Time PCR (qRT-PCR) analysis using TaqMan assay and by ASE assays using dHPLC-based primer extension.Twenty out of 49 patients showed germline mutations: 14 in APC gene and six in MUTYH gene. Twenty-nine patients did not show mutations in both genes. Results from qRT-PCR indicated that gene expression of both APC and MUTYH was reduced in patients analyzed. In particular, a significant reduction in APC expression was observed in patients without APC germline mutation vs control group (P?<?0.05) while APC expression in the mutation carrier patients, although lower compared to control individuals, did not show statistical significance. On the other hand a significant reduced MUTYH expression was detected in patients with MUTYH mutations vs control group (P?<?0.05). Altered ASE of APC was detected in four out of eight APC mutation carriers. In particular one case showed a complete loss of one allele. Among APC mutation negative cases, 4 out of 13 showed a moderate ASE. ASE of MUTYH did not show any altered expression in the cases analyzed. Spearman's Rho Test analysis showed a positive and significant correlation between APC and MUTYH genes both in cases and in controls (P?=?0.020 and P?<?0.001).APC and MUTYH showed a reduced germline expression, not always corresponding to gene mutation. Expression of APC is decreased in mutation negative cases and this appears to be a promising indicator of FAP predisposition, while for MUTYH gene, mutation is associated to reduced mRNA expression. This study could improve the predictive genetic diagnosis of at-risk individuals belonging to families with reduced mRNA expression regardless of presence of mutation.

Dataset Information

Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population.

Publications

Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population.

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