Association of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha Coding Variants with Hepatocellular Carcinoma Risk in the Moroccan Population: A Case-Control Study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) plays a crucial role in regulating the biogenesis of mitochondria. We aimed to assess the association between PPARGC1A polymorphisms and HCC risk in a Moroccan population. METHODS: In this case-control study, 147 patients with HCC and 147 controls without pre-existing liver disease were matched for ethnicity. TaqMan SNP allelic discrimination assays were used for genotyping of PPARGC1A rs8192678 and rs12640088 polymorphisms. RESULTS: The result revealed that individuals with the GA/AA genotypes for rs8192678 had a significantly higher risk of HCC compared to those with the GG genotype (OR=6.68; P<0.0001, and OR=9.78; P<0.0001, respectively). In particular, the A allele of rs8192678 was over-represented in HCC patients compared to controls (40% versus 12%, P<0.0001, respectively). With respect to PPARGC1A rs12640088 variant, two genetic models (codominant and dominant) were tested to explore any potential variations in the distribution of SNP A>C among HCC cases and control subjects group. Overall, no significant association between rs12640088 and HCC was found (P>0.05). Interestingly, a significantly higher level of aspartate aminotransferase was observed in HCC patients with GG-GA genotypes (280 IU/L) compared to those with GG genotype (164 IU/L) at rs8192678 (P=0.0019). CONCLUSION: Our results suggest that the PPARGC1A rs8192678 polymorphism is associated with an increased risk of HCC in Moroccan population and may serve as a prognostic marker for liver cancer.

Epidemiological characteristics of acute hepatitis A, 2013-2016: a cross-sectional study in Morocco.

BACKGROUND: Hepatitis A virus (HAV) is the common cause of acute hepatitis worldwide. Indeed, hepatitis A is endemic in developing countries such in Morocco and most residents are exposed in childhood. The characterisation of circulating strains of HAV remains crucial to understand the virological evolution and geo-temporal characteristics, which are essential for controlling infections and outbreaks. The purpose of the current study was the detection and characterisation of HAV strains circulating in Morocco by performing serological test, RT-PCR, sequencing and phylogenetic analysis. METHODS: In this cross-sectional study, 618 suspected acute hepatitis cases were examined by Architect HAV abIgM. Of the 162 positives, 64 underwent RNA extraction. None of the suspected cases was immune to HAV and none of them had received a blood transfusion. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and the VP1/VP3 capsid region of HAV were subjected to sequencing and phylogenetic analyses. RESULTS: HAV Acute infection rate was 26.2% [95% CI, 22.8-29.9], while viraemia reached 45% (29/64) after amplification of the VP3/VP1 region. Phylogenetic analysis of the VP1/2A segment revealed the presence of sub-genotypes IA and IB. Eighty-seven percent of the strains belonged to the subgenotype IA, while twelve percent to IB subgenotype. CONCLUSION: This first molecular study of acute hepatitis A in Morocco provided information about genetic diversity of HAV, revealing the co-circulating of only two subgenotypes (IA and IB). Notably, subgenotype IA was found to be the predominant subgenotype in Morocco.

Programmed cell death-1 3'-untranslated region polymorphism is associated with spontaneous clearance of hepatitis B virus infection.

Hepatitis B virus (HBV)-specific CD8+ T cells play an important role in the clearance of HBV infection. Programmed cell death-1 (PD-1), an immunosuppressive molecule that regulates T-cell activation and peripheral immune tolerance, is increasingly shown to influence the outcome of HBV infection. rs10204525, a single-nucleotide polymorphism in the 3'-untranslated region (3'-UTR) of PD-1, has been associated with susceptibility and disease progression of chronic HBV infection in far-eastern patients. The aim of our study was to assess the impact of rs10204525 variation on HBV infection in Moroccan patients. A total of 236 patients with chronic HBV infection and 134 individuals with spontaneous HBV resolution were genotyped using a Taqman assay. In addition, PD-1 mRNA expression in peripheral blood nuclear cells was determined by quantitative reverse-transcription polymerase chain reaction. We found that the AA genotype is protective (odds ratio, 0.43; 95% confidence interval, 0.19 to 0.97; P = 0.038) against HBV infection. Interestingly, PD-1 messenger RNA (mRNA) expression analysis has revealed that chronic HBV carriers with GG and GA displayed higher levels of PD-1 mRNA compared with corresponding genotypes in resolved subjects (P = 0.031 and 0.014, respectively). Our data suggest that Mediterranean HBV-infected patients carrying PD-1 GG and GA genotypes at rs10204525 have high PD-1 mRNA expression and may be more prone to installation of chronicity.

Interleukin 28B rs12979860 genotype and Human Immunodeficiency Virus type 1: Susceptibility, AIDS development and therapeutic outcome.

Human Immunodeficiency Virus type 1 (HIV-1) infection and progression varies widely among individuals. Interferon-λ3 exerts anti-HIV function by activating JAK/STAT pathway-mediated innate immunity. Therefore, we aimed to investigate the association between single nucleotide polymorphisms of the interleukin 28B (IL28B) gene, and the risk of acquisition, AIDS development and therapeutic outcome of HIV-1 in a Moroccan population. A total of 266 HIV-1 seropositive and 158 HIV-1 seronegative subjects were enrolled. Genotyping of rs12979860 of the IL28B was performed using a predesigned TaqMan SNP genotyping assay. No significant association was found between IL28B rs12979860 polymorphism and susceptibility to HIV-1 infection and AIDS development (p > .05). However, in HIV-1 treated patients carrying CC genotype had a more pronounced high levels of CD4+ T-cell compared to subjects with TT genotype (p = .0004). Interestingly, regarding HIV-1 viral load no significant differences between IL28B genotypes in treated and untreated patients were observed (p < .05). IL28B rs12979860 polymorphism not influences the susceptibility to HIV-1 and the AIDS development. However, this polymorphism may affect the response to treatment as measured by CD4+ T cell counts.