Programmed cell death-1 single-nucleotide polymorphism rs10204525 is associated with human immunodeficiency virus type 1 RNA viral load in HIV-1-infected Moroccan subjects.

Human Immunodeficiency Virus (HIV-1) infections are characterized by dysfunctional cellular and humoral antiviral immune responses. The progressive loss of effector functions in chronic viral infection has been associated with the up-regulation of programmed death-1 (PD-1), a negative regulator of activated T cells and Natural Killer cells. In HIV-1 infection, increased levels of PD-1 expression correlate with CD8 + T-cell exhaustion. In vitro, PD-1 blockade using PD-1 antibodies led to an increase in HIV-1 specific CD8 + T and memory B cell proliferation. We aimed to investigate the impact of PDCD1 rs10204525 polymorphism on HIV-1 susceptibility, AIDS development, and treatment response outcomes in HIV-1 infection in a Moroccan population. A total of 214 HIV-1 seropositive and 250 seronegative subjects were enrolled to investigate the association between the between the single-nucleotide polymorphism (SNP) rs10204525 of PDCD1 gene and HIV-1 pathogenesis using a predesigned TaqMan SNP genotyping assay. No significant association was found between rs10204525 and susceptibility to HIV-1 infection and AIDS development (p > 0.05). Genotype frequencies were significantly associated with the viral load before ART (p = 0.0105). HIV-1 viral load was significantly higher among subjects with the CC compared to TT genotype (p = 0.0043). In treated subjects, the median of viral load levels was significantly higher in CC and CT groups than TT subjects (p < 0.005). However, analysis of the correlation between CD4 + T-cell levels and PDCD1 polymorphism before and after ART showed no significant difference (p > 0.05). Our results demonstrated that rs10204525 polymorphism does not affect HIV-1 infection. However, this polymorphism may affect the response to treatment as measured by RNA viral load levels.

Lack of Association between IFNL3 Polymorphism and Human Papillomavirus Infection and Their Progression in HIV-Infected Women Receiving Antiretroviral Treatment.

BACKGROUND: It has been reported that interferon-λ3 (IFNL3)might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of IFNL3 single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the IFNL3 region and HPV infection in women with human immunodeficiency virus (HIV) infection. METHODS: A total of 236 HIV patients, including 65 HPV-negative and 171 HPV DNA-positive women, were enrolled into this study. The IFNL3 rs12979860 polymorphism was genotyped using a predesigned TaqMan SNP genotyping assay. RESULTS: Data showed no significant differences in genotypes or allele frequencies between the HPV DNA-positive and the HPV-negative women (p > 0.05). After dividing the HPV-positive women according to cytology results into patients with abnormal and normal lesions, the genotype and allele distribution of the SNP did not significantly differ between the 2 groups (p > 0.05). CONCLUSIONS: Our results showed that the IFNL3 rs12979860 polymorphism is not a major determinant of the susceptibility to HPV infection and their progression to abnormal cervical lesions in women living with HIV.

Lack of Ser267Phe variant of sodium taurocholate cotransporting polypeptide among Moroccans regardless of hepatitis B virus infection status.

BACKGROUND: The sodium taurocholate co-transporting polypeptide, encoded by SLC10A1, was identified as a functional receptor for hepatitis B virus (HBV). The objective of this study was to determine if there was an association of the Ser267Phe variant (rs2296651) with HBV infection status in Moroccan patients. METHODS: Using a TaqMan 5' allelic discrimination assay, the Ser267Phe variant was genotyped in 286 chronic hepatitis B patients, 135 individuals with spontaneous clearance from HBV infection and 109 healthy controls negative for hepatitis B serological markers. RESULTS: In this cohort, we detected only wild-type genotype (S267S) in all groups. This polymorphism was not associated with the HBV infection status in Moroccan patients. CONCLUSIONS: The S267F variant is absent among Moroccans regardless of chronic HBV infection status.

Molecular characterization of hepatitis C virus core region in moroccan intravenous drug users.

Intravenous drug users (IDUs) represent a highly-infected reservoir for Hepatitis C virus (HCV) worldwide, harboring some of the most elevated prevalences and majority of the epidemic in developed nations. Studies aimed at sequencing regions of the viral genome uncovered amino acid mutations, some of which have been implicated in resistance to standard of care pegylated interferon/Ribavirin double therapy. Using the nested PCR method on the Core region of HCV strains in Moroccan IDUs living in the Tangier region this study sought to identify genotype-specific amino acid mutations, followed by Phylogenetic methods in order to compare them with international strains so as to identify sequences of highest homology. Genotyping was confirmed and recombination events excluded by line-probe assay. Italy was found most homologous for genotypes 1a and 3a, Iran for genotype 1a and Egypt for genotype 4a. Amino Acid Mutation analysis revealed the following novel genotype 3a-specific mutations: N16I, L36V, T49A, P71S, T75S, and T110N. The outcome of this work describes the HCV genetic heterogeneity in high-risk intravenous drug users, and it gives clues to the global migratory flow of genotypes as they cross geographical boundaries between various IDU populations and identifies "signature" amino acid mutations traceable to HCV genotype 3a. Identification of key amino acid positions in the HCV Core region with higher rates of mutations paves the way for eventual clinical trials seeking to establish a link between these recurrent mutations and response to standard of care Interferon and Ribavirin antiviral therapy. J. Med. Virol. 88:1376-1383, 2016. © 2016 Wiley Periodicals, Inc.

Stabilization of the integrase-DNA complex by Mg2+ ions and prediction of key residues for binding HIV-1 integrase inhibitors.

The HIV-1 integrase is an attractive target for the therapeutics development against AIDS, as no host homologue of this protein has been identified. The integrase strand transfer inhibitors (INSTIs), including raltegravir, specifically target the second catalytic step of the integration process by binding to the DDE motif of the catalytic site and coordinating Mg(2+) ions. Recent X-ray crystallographic structures of the integrase/DNA complex from prototype foamy virus allowed to investigate the role of the different partners (integrase, DNA, Mg(2+) ions, raltegravir) in the complex stability using molecular dynamics (MD) simulations. The presence of Mg(2+) ions is found to be essential for the stability, whereas the simultaneous presence of raltegravir and Mg(2+) ions has a destabilizing influence. A homology model of HIV-1 integrase was built on the basis of the X-ray crystallographic information, and protein marker residues for the ligand binding were detected by clustering the docking poses of known HIV-1 integrase inhibitors on the model. Interestingly, we had already identified some of these residues to be involved in HIV-1 resistance mutations and in the stabilization of the catalytic site during the MD simulations. Classification of protein conformations along MD simulations, as well as of ligand docking poses, was performed by using an original learning method, based on self-organizing maps. This allows us to perform a more in-depth investigation of the free-energy basins populated by the complex in MD simulations on the one hand, and a straightforward classification of ligands according to their binding residues on the other hand.

Discovery of naturally occurring transmissible chronic hepatitis B virus infection among Macaca fascicularis from Mauritius Island.

UNLABELLED: Despite a high prevalence of hepatitis B virus (HBV) infection in endangered apes, no HBV infection has been reported in small, old-world monkeys. In search for a small, nonhuman primate model, we investigated the prevalence of HBV infection in 260 macaque (Cercopithecidae) sera of various geographical origins (i.e., Morocco, Mauritius Island, and Asia). HBV-positive markers were detected in cynomolgus macaques (Macaca fascicularis) from Mauritius Island only, and, remarkably, HBV DNA was positive in 25.8% (31 of 120) and 42% (21 of 50) of serum and liver samples, respectively. Strong liver expression of hepatitis B surface antigen and hepatitis B core antigen was detected in approximately 20%-30% of hepatocytes. Furthermore, chronic infection with persisting HBV DNA was documented in all 6 infected macaques during an 8-month follow-up period. Whole HBV genome-sequencing data revealed that it was genotype D subtype ayw3 carrying substitution in position 67 of preS1. To confirm infectivity of this isolate, 3 Macaca sylvanus were inoculated with a pool of M. fascicularis serum and developed an acute HBV infection with 100% sequence homology, compared with HBV inoculum. We demonstrated the presence of a chronic HBV infection in M. fascicularis from Mauritius Island. This closely human-related HBV might have been transmitted from humans, because the initial breeding colony originated from very few ancestors 300 years ago when it was implemented by Portuguese who imported a handful of macaques from Java to Mauritius Island. CONCLUSION: This report on natural, persisting HBV infection among cynomolgus macaques provides the first evidence for the existence of a novel, small simian model of chronic HBV infection, immunologically close to humans, that should be most valuable for the study of immunotherapeutic approaches against chronic hepatitis B.

Meta-analysis of MTHFR C677T polymorphism and type 2 diabetes mellitus in MENA region.

BACKGROUND AND AIMS: The association of the C677T polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) gene with susceptibility to type 2 diabetes mellitus (T2DM) has been widely debated. Therefore, our aim is to conclusively resolve this controversy in the Middle East and North Africa region population through a meta-analysis. MATERIEL AND METHODS: We identified relevant articles by searching literature databases, such as PubMed, Web of Science, and Science Direct, to retrieve studies that examined the association between the MTHFR C677T polymorphism and the risk of developing T2DM. Using meta-analysis, we calculated the odds ratio (OR) and confidence interval (CI) values of these studies to assess the susceptibility to T2DM related to the C677T polymorphism of MTHFR gene. RESULTS: In this meta-analysis, we included a total of 13 publications comprising 2072 T2DM patients and 2164 control subjects. The results of the meta-analysis suggested that there is a significant association between the C677T polymorphism and T2DM risk in overall comparisons for allele contrasts (T vs C): OR = 1.25, 95% CI = 1.04-1.50, p = 0.015 and homozygous (TT vs CC): OR = 1.44, 95% CI = 1.01-2.05, p = 0.038). Subgroup analysis revealed that the C677T polymorphism is associated with a risk of T2DM in Asian populations, while there is no significant association between this polymorphism and T2DM in Caucasian and African populations. Furthermore, there was no evidence of publication bias. CONCLUSION: Our study's results suggest that the allele contrast of the C677T polymorphism of the MTHFR gene is associated with an increased risk of T2DM in the overall population, particularly among Asians.

Computational analysis of structural and functional evaluation of the deleterious missense variants in the human CTLA4 gene.

CTLA-4 is an immune checkpoint receptor that negatively regulates the T-cell function expressed after T-cell activation to break the immune response. The current study predicted the genomic analysis to explore the functional variations of missense SNPs in the human CTLA4 gene using PolyPhen2, SIFT, PANTHER, PROVEAN, Fathmm, Mutation Assessor, PhD-SNP, SNPs&GO, SNAP2, and MutPred2. Phylogenetic conservation protein was predicted by ConSurf. Protein structural analysis was carried out by I-Mutant3, MUpro, iStable2, PremPS, and ERIS servers. Molecular dynamics trajectory analysis (RMSD, RMSF, Rg, SASA, H-bonds, and PCA) was performed to analyze the dynamic behavior of native and mutant CTLA-4 at the atomic level. Our in-silico analysis suggested that C58S, G118R, P137Q, P137R, P137L, P138T, and G146L variants were predicted to be the most deleterious missense variants and highly conserved residues. Moreover, the molecular dynamics analysis proposed a decrease in the protein stability and compactness with the P137R and P138T highlighting the impact of these variants on the function of the CTLA-4 protein.Communicated by Ramaswamy H. Sarma.

Association between Methylene-Tetrahydrofolate Reductase C677T Polymorphism and Human Immunodeficiency Virus Type 1 Infection in Morocco.

Human immunodeficiency virus type 1 (HIV-1) infection varies substantially among individuals. One of the factors influencing viral infection is genetic variability. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been correlated with different types of pathologies, including HIV-1. The MTHFR gene encodes the MTHFR enzyme, an essential factor in the folate metabolic pathway and in maintaining circulating folate and methionine at constant levels, thus preventing the homocysteine accumulation. Several studies have shown the role of folate on CD4+ T lymphocyte count among HIV-1 subjects. In this case-control study we aimed to determine the association between the MTHFR C677T polymorphism and HIV-1 infection susceptibility, AIDS development, and therapeutic outcome among Moroccans. The C677T polymorphism was genotyped by polymerase chain reaction followed by fragment length polymorphism digestion in 214 participants living with HIV-1 and 318 healthy controls. The results of the study revealed no statistically significant association between MTHFR C677T polymorphism and HIV-1 infection (P > .05). After dividing HIV-1 subjects according to their AIDS status, no significant difference was observed between C677T polymorphism and AIDS development (P > .05). Furthermore, regarding the treatment response outcome, as measured by HIV-1 RNA viral load and CD4+ T cell counts, no statistically significant association was found with MTHFR C677T polymorphism. We conclude that, in the genetic context of the Moroccan population, MTHFR C677T polymorphism does not affect HIV-1 infection susceptibility, AIDS development, or response to treatment. However, more studies should be done to investigate both genetic and nutritional aspects for more conclusive results.

MBL2 gene polymorphisms related to HIV-1 infection susceptibility and treatment response.

Human Mannose-binding lectin (MBL) is a protein encoded by MBL2 gene involved in the activation of the lectin-complement pathway. Several studies emphasized the role of MBL2 gene in several infectious diseases' susceptibility, including HIV-1 infection. We aim to investigate the impact of 10 MBL2 gene polymorphisms located in the promoter, 5'UTR and exon 1 regions on HIV-1 physiopathology. The polymorphisms genotyping of 400 individuals, which 200 were HIV-1 positive patients and 200 were controls, was performed by PCR-sequencing. Our results showed that rs503037 and rs1800451 polymorphisms are associated with a high risk of HIV-1 infection susceptibility while rs7096206 and rs11003123 showed a protective effect. A significant association between haplotype CGA and HIV-1 infection susceptibility was also found in the exon 1 region. Moreover, rs11003124, rs7084554, rs36014597 and rs11003123 polymorphisms revealed an association with treatment response outcome as measured by RNA viral load. This study highlights the importance of MBL2 polymorphisms in the modulation of HIV-1 infection susceptibility and the contribution to treatment response outcomes among Moroccan subjects.

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis.

BACKGROUND AND AIMS: The association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region). MATERIAL AND METHODS: Our data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression. RESULTS: Of 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33-2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27-3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54-3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78-6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07-2.88; p = 0.024). CONCLUSION: Our result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.

Prevalence and risk factors of chronic complications among patients with type 2 diabetes mellitus in Morocco: a cross-sectional study.

Introduction: microvascular and macrovascular complications of type 2 diabetes mellitus (T2DM) are one of the major causes of morbidity and mortality worldwide among patients with T2DM. This study aims to estimate the prevalence of these chronic complications and identify the associated risk factors among Moroccan patients with T2DM. Methods: this cross-sectional study was conducted on 505 T2DM patients followed by the healthcare Centers of the Casablanca-Settat region from January 2017 to July 2018. The socio-demographic, anthropometric, biochemical, and clinical data were recorded using a structured survey. For statistical analysis, SPSS version 20 is used. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with chronic complications of T2DM. Results: among the 505 Moroccan patients with T2DM, 84.98% were women. The average age of the patients was 57.27±10.74 years. Diabetic eye disease was the most frequent complication (29.5%) followed by cardiovascular diseases (CVDs) (22.4%), kidney disease in diabetes (9.8%), diabetes foot (2.8%), and neuropathy (1.8%). Logistic regression analysis showed that the CVDs was associated with hypertension (OR: 2.41; 95% CI: 1.11-5.22; p=0.026), hypolipidemia treatment (OR: 2.20; 95% CI: 1.06-4.59; p=0.034), insulin use (OR= 0.39; 95%CI: 0.15-0.96, p=0.043) and LDL-C (OR: 1.01; 95% CI: 1-1.02; p=0.035) in T2DM patients. However, the major risk factors for the development of kidney disease in T2DM patients were a lack of regular physical activity (OR: 3.77; 95% CI: 1.22-11.67; p=0.021), hypolipidemia treatment (OR: 8.31; 95% CI: 1.86-36.97; p=0.005), and high serum creatinine (OR: 1.33; 95% CI: 1.16-1.53; p≤0.001). In addition, LDL-C levels were found to be a significant risk factor for diabetes eye disease (OR: 1.01; 95% CI: 1.00-1.03; p=0.008). Conclusion: this study shows that the increased duration of diabetes, insulin use, lack of regular physical exercise, hypertension, hypolipidemia treatment, high serum creatinine, and LDL-C were significant risk factors for chronic complications of T2DM in Moroccan patients.

Prevalence of dyslipidemia and the relationship between HbA1C and lipid profile in Moroccan patients with T2DM: a cross-sectional study.

Introduction: the increased prevalence of dyslipidemia in patients with type 2 diabetes mellitus (T2DM) results from uncontrolled hyperglycemia and consistently contributes to an elevated risk of cardiovascular complications. This study sought to estimate the prevalence of dyslipidemia and to investigate the relationship between glycated hemoglobin (HbA1C) and serum lipid levels in Moroccan patients with T2DM. Methods: a total of 505 patients with T2DM were included in this cross-sectional study, 77.4% with chronic complications and 22.6% without. The collected data were examined using statistical package for the social sciences (SPSS) version 20.0 software and appropriate statistical methods. Results: the data analysis showed that the mean and SD of age were 57.27±10.74 years. Among 505 patients with T2DM, the prevalence of hypercholesterolemia, hypertriglyceridemia, increased low-density lipoprotein cholesterol (LDL-C), and decreased HDL-C was 41.4%, 35.9%, 27.1%, and 17%, respectively. In addition, the data analysis showed that levels of total cholesterol (TC) (p≤0.001), triglycerides (p≤0.001), Low-density lipoprotein cholesterol (LDL-C) (p≤0.001), TC/HDL-C ratio (p=0.006), and LDL-C/HDL-C ratio (p=0.006) were significantly higher in T2DM patients with complications as compared to those without complications. The patients with HbA1C > 7.0% had significantly higher values of fasting blood glucose (FBG) (p≤0.001), total cholesterol (p≤0.001), triglycerides (p≤0.001), and TC/HDL-C ratio (p=0.025) as compared to the patients with HbA1C ≤ 7.0%. The HbA1C demonstrated a significant negative correlation with age (r=-0.139), and positive correlation with FBG (r=0.673), total cholesterol (r=0.189) and triglycerides (r=0.243). Conclusion: our results showed that HbA1C is the most important biomarker of long-term glycemic control and can also be a good indicator of the lipid profile.

In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection.

SARS-CoV-2 coronavirus uses for entry to human host cells a SARS-CoV receptor of the angiotensin-converting enzyme (ACE2) that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of ACE2 missense variants on protein structure, stability, and function, various bioinformatics tools were used including SIFT, PANTHER, PROVEAN, PolyPhen2.0, I. Mutant Suite, MUpro, SWISS-MODEL, Project HOPE, ModPred, QMEAN, ConSurf, and STRING. All twelve ACE2 nsSNPs were analyzed. Six ACE2 high-risk pathogenic nsSNPs (D427Y, R514G, R708W, R710C, R716C, and R768W) were found to be the most damaging by at least six software tools (cumulative score between 6 and 7) and exert deleterious effect on the ACE2 protein structure and likely function. Additionally, they revealed high conservation, less stability, and having a role in posttranslation modifications such a proteolytic cleavage or ADP-ribosylation. This in silico analysis provides information about functional nucleotide variants that have an impact on the ACE2 protein structure and function and therefore susceptibility to SARS-CoV-2.

Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2.

The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.

The Biological Significance of Long noncoding RNAs Dysregulation and their Mechanism of Regulating Signaling Pathways in Cervical Cancer.

Despite the remarkable decrease in cervical cancer incidence due to the availability of the HPV vaccine and implementation of screening programs for early detection in developed countries, this cancer remains a major health problem globally, especially in developing countries where most of the cases and mortality occur. Therefore, more understanding of molecular mechanisms of cervical cancer development might lead to the discovery of more effective diagnosis and treatment options. Research on long noncoding RNAs (lncRNAs) demonstrates the important roles of these molecules in many physiological processes and diseases, especially cancer. In the present review, we discussed the significance of lncRNAs altered expression in cervical cancer, highlighting their roles in regulating highly conserved signaling pathways, such as mitogen-activated protein kinase (MAPK), Wnt/ß-catenin, Notch, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways and their association with the progression of cervical cancer in order to bring more insight and understanding of this disease and their potential implications in cancer diagnosis and therapy.

An assessment of toll-like receptor 7 and 8 gene polymorphisms with susceptibility to HIV-1 infection, AIDS development and response to antiretroviral therapy.

Toll-like receptors (TLRs) play an important role in activating the innate immune response, inducing inflammation and initiating the adaptive immune response. In this study, we assess the influence of TLR7 and TLR8 gene polymorphisms on HIV-1 susceptibility, AIDS development, and treatment outcomes. The TLR7 and TLR8 single nucleotide polymorphisms (SNPs) were genotyped through real-time PCR in 222 patients living with HIV-1 and 141 healthy controls. Frequencies of the TLR7-IVS2-151 G/A and TLR7-IVS1 + 1817 G/T genotypes and alleles were not significantly increased in patients with HIV-1 infection compared to healthy controls both in males and females. Whereas, males carrying TLR8 Met allele were twice susceptible to HIV-1 infection compared to subjects with A allele (OR = 2.04, 95 % CI 1.10-3.76; p = 0.021). Interestingly, for TLR8-129 G/C, both males and females carrying G allele and GG genotype, respectively were significantly associated with HIV-1 infection (p < 0.0001). Moreover, the TLR7 IVS1 + 1817 G/T and the TLR8 rs3764880 were associated with protection to progress the AIDS stage in male and female, respectively (p < 0.05). Males carrying TLR7 IVS2-151-A allele showed a significant increased level of HIV-1 viral load pre-treatment, in comparison with individuals carrying the G allele (p-value = 0.036). Additionally, males carrying TLR8 Met allele showed statistically higher HIV viral load at baseline (p-value = 0.04) and after treatment (p-value = 0.013). Regarding CD4 + T cell counts, no significant association was found with TLR7 and TLR8 SNPs before and after antiretroviral treatment. This data demonstrates that TLR8 polymorphisms could affect HIV-1 infection. Moreover, an association between TLR7 IVS2-151-A and TLR8 Met alleles and plasma HIV viral load level was found.

Carrier frequencies of mutations/polymorphisms in the connexin 26 gene (GJB2) in the Moroccan population.

Mutations in the Connexin 26 gene (GJB2/Cx26) are responsible for more than half of all cases of prelingual nonsyndromic recessive deafness in Caucasians. The carrier frequency of the 35delG-GJB2 mutation was found to be as high as 2-4% in the Mediterranean populations. Different GJB2 mutations were reported in the Moroccan patients with autosomal recessive nonsyndromic hearing loss; however, rare studies were carried out on the carrier frequencies of these mutations in the healthy populations. The aim of this study was to estimate the carrier frequencies of the GJB2 mutations in the Moroccan population. The molecular analysis of the 35delG mutation and other GJB2 sequence variations was performed in 386 healthy unrelated Moroccan individuals with no known hearing loss. Five GJB2 sequence variations at heterozygous state were found: two mutations, 35delG and 109G > A (V37I), and three polymorphisms, 79G > A (V27I), 341G > A (E114G), and 457G > A (V153I). The carrier frequency of the 35delG mutation was the highest with 2.07% [95% confidence interval (0.90-4.04%)], followed by that of the V37I mutation with 1.43% (0.06-5.39). The carrier frequency of V27I, E114G, and V153I changes was estimated to be 0.71% (0.01-4.34). This finding shows that the 35delG carrier frequency found here is similar to the one observed in Mediterranean populations. It provides new information about GJB2 carrier rates facilitating the diagnosis and the genetic counseling in the Moroccan population.

Prostate-specific Antigen Levels in Moroccan Diabetic Males: A Cross-sectional Study.

BACKGROUND: Recent studies have shown an inverse relationship between diabetes and prostate- specific antigen (PSA) levels. OBJECTIVE: This study aimed to evaluate the PSA levels in the serum of diabetic and non-diabetic Moroccan males. METHODS: In a cross-sectional study, four hundred and seventy diabetic and 869 non-diabetic males were screened from January 2015 to April 2016 at Pasteur institute of Morocco. Hemoglobin A1c and Fasting Blood Glucose were measured using high performance liquid chromatography and dry chemistry, respectively. We used a chemiluminescent microparticle immunoassay technology to evaluate the levels of Serum PSA and testosterone. RESULTS: Overall, the PSA levels revealed no significant difference between diabetic and non-diabetic males (1.31 ± 0.04ng/mL vs.1.36 ± 0.03ng/mL, p = 0.380, respectively). The PSA levels increased with age both in non-diabetics and diabetics. Moreover, in diabetic subjects, the PSA levels were less age dependent (p =0.002) than in non-diabetic (p < 0.0001). The stratified analysis showed that the PSA was significantly lower in diabetic than in non-diabetic subjects aged between 50-59 years (p= 0.0004). Furthermore, no significant testosterone concentrations were observed in the subjects with or without diabetes (p= 0.904). CONCLUSION: Our results show that the PSA levels are age-dependant in diabetic and non-diabetic males but the PSA levels are affected by diabetes status only in the group aged between 50-59 years.

An Unusual Case of Gullo's Syndrome Concomitant with Serious Endometriosis Disease in a Postmenopausal Woman.

Gullo's syndrome is a singular physiological phenomenon defined by an abnormal increase in serum pancreatic enzyme levels that may occur in healthy subjects in the absence of pancreatic disorders. During routine health examination in a 54-year-old postmenopausal woman with severe endometriosis, elevated values of serum amylase and lipase were fortuitously observed (198 and 1461 U/L, resp.). Over five years of regular pancreas surveillance, all clinical, biological, and imaging investigations were normal. However, the pancreatic enzyme levels have shown considerable fluctuations including some episodic transient normalization. The description of this benign pancreatic hyperenzymemia case incidentally associated with endometriosis disease is a very rare clinical situation. More in-depth documentation of this phenomenon may help clinicians to avoid unnecessary diagnostic management approaches and reassure the concerned patients that this affection would not be so worrying.