Mannose-Binding Lectin Gene Variants as Disease Susceptibility Biomarkers in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by progressive destruction of peripheral joints. About 1% of the human population worldwide is suffering from this disease. The pathophysiology of RA is largely being influenced by immune dysregulation. Mannose-binding lectin (MBL), an acute-phase protein, has been reported to play an important role in pathogenesis of RA by the activation of complement pathway. Various studies documented the established the role of MBL in pathogenesis of various autoimmune diseases, including RA. MBL protein is encoded by gene MBL2, mapped on chromosome 10q11.2-q21. Objective: Both MBL serum levels and activity are mainly determined genetically by its variants. So considering the putative clinical role of MBL2, this case-control association study was designed to assess its six functional variants in a northwestern Indian cohort. Methods: Genetic typing of six MBL2 variants was done by amplification refractory mutation system-polymerase chain reaction. Data were analyzed using suitable statistical tools. Results: Significant difference has been observed in genotypic and allelic distribution between cases and controls for rs11003125. Comparison of allelic distribution for rs1800450 showed significantly high prevalence of A allele in cases than controls. Conclusion: These results indicate that MBL2 variants may act as plausible marker for susceptibility toward RA. Keeping this in view, it is pertinent to screen these variants in other population groups of India.

Genetic determinants of complement activation in the general population.

Complement is a fundamental innate immune response component. Its alterations are associated with severe systemic diseases. To illuminate the complement's genetic underpinnings, we conduct genome-wide association studies of the functional activity of the classical (CP), lectin (LP), and alternative (AP) complement pathways in the Cooperative Health Research in South Tyrol study (n = 4,990). We identify seven loci, encompassing 13 independent, pathway-specific variants located in or near complement genes (CFHR4, C7, C2, MBL2) and non-complement genes (PDE3A, TNXB, ABO), explaining up to 74% of complement pathways' genetic heritability and implicating long-range haplotypes associated with LP at MBL2. Two-sample Mendelian randomization analyses, supported by transcriptome- and proteome-wide colocalization, confirm known causal pathways, establish within-complement feedback loops, and implicate causality of ABO on LP and of CFHR2 and C7 on AP. LP causally influences collectin-11 and KAAG1 levels and the risk of mouth ulcers. These results build a comprehensive resource to investigate the role of complement in human health.

Focused panel sequencing points to genetic predisposition in non-cirrhotic intrahepatic portal hypertension patients in India.

OBJECTIVE: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. METHODS: In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme - a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. RESULT: Eighty-four Indian patients with liver biopsy-proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. CONCLUSION: In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.

The MBL2 genotype relates to COVID-19 severity and may help to select the optimal therapy.

OBJECTIVES: Sars-CoV-2 acute infection is clinically heterogeneous, ranging from asymptomatic cases to patients with a severe, systemic clinical course. Among the involved factors age and preexisting morbidities play a major role; genetic host susceptibility contributes to modulating the clinical expression and outcome of the disease. Mannose-binding lectin is an acute-phase protein that activates the lectin-complement pathway, promotes opsonophagocytosis and modulates inflammation, and is involved in several bacterial and viral infections in humans. Understanding its role in Sars-CoV-2 infection could help select a better therapy. METHODS: We studied MBL2 haplotypes in 419 patients with acute COVID-19 in comparison to the general population and related the haplotypes to clinical and laboratory markers of severity. RESULTS: We recorded an enhanced frequency of MBL2 null alleles in patients with severe acute COVID-19. The homozygous null genotypes were significantly more frequent in patients with advanced WHO score 4-7 (OR of about 4) and related to more severe inflammation, neutrophilia, and lymphopenia. CONCLUSIONS: Subjects with a defective MBL2 genotype (i.e., 0/0) are predisposed to a more severe acute Sars-CoV-2 infection; they may benefit from early replacement therapy with recombinant MBL. Furthermore, a subset of subjects with the A/A MBL genotype develop a relevant increase of serum MBL during the early phases of the disease and develop a more severe pulmonary disease; in these patients, the targeting of the complement may help. Therefore, COVID-19 patients should be tested at hospitalization with serum MBL analysis and MBL2 genotype, to define the optimal therapy.

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups.

Introduction: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood. Methods: We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome. Results: We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID. Conclusion: In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.

MBL2 gene variants and susceptibility to meningitis in Egyptian patients.

BACKGROUND: Meningitis is inflammation of the membranes enclosing the brain and spinal cord. It is a fatal disease with severe morbidity and mortality. Mannose binding lectin (MBL) encoded by MBL2 gene activates complement system through lectin pathway in innate immunity to defense against the infections. OBJECTIVE: The current study aimed to investigate the promoter and exon 1 variants of MBL2 gene among Egyptian patients having meningitis to explore their role in disease susceptibility. PATIENTS AND METHODS: This case-control study, included 53 patients and 50 sex and age matched controls. MBL2 genotyping was done using Sanger sequencing. RESULTS: The frequency of one promoter (c.-290C > G) and four in exon 1 (c.161G > A, c.170G > A, c.154C > T and c.132C > T) as well as another one located in its 5'utranslated part (c.-66C > T) variants were estimated. The incidence of the four individual exonic variants was not significantly different between cases and healthy individuals (all P > 0.05). The promoter variant, c.-290C > G was found in all examined patients (84.9% of the patients in homozygote state and 15.1% of patients in heterozygous state) with a highly significant variance in the prevalence of this variant between cases and control group (p = 0.0001). Additionally, UTR variant (c.-66C > T) was also significantly higher in patients than controls (P = 0.033).In comparison with clinical outcome, it was found that c.170G > A variant named C allele was associated with favorable outcome in the studied patients (P = 0.025). CONCLUSION: The results obtained showed that the Promoter (c.-290C > G) and UTR (c.-66C > T) variants of MBL2 gene may be potential risk factors for disease susceptibility in Egyptian cases with meningitis. Our results also proposed that c.170G > A (C allele and CC genotype) could affect the severity and play a protective role in these patients. The other genetic variants of MBL2 gene, including c.132C > T, c.161G > A (A > B), and c.154C > T (A > D) that were investigated, did not show any association with susceptibility or severity of meningitis.

Evaluation of Beta-Defensin 1 and Mannose-Binding Lectin 2 Polymorphisms in Children with Dental Caries Compared to Caries-Free Controls: A Systematic Review and Meta-Analysis.

Background and objective: Some variants in defensin beta 1 (DEFB1) and mannose-binding lectin 2 (MBL2) genes can be associated with oral diseases. Herein, we designed a systematic review and meta-analysis to evaluate the association of DEFB1 (rs11362, rs1799946, and rs1800972) and MBL2 (rs7096206 and rs1800450) polymorphisms with the susceptibility to dental caries (DC) in children. Materials and methods: A systematic literature search was conducted in the PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases until 3 December 2022, without any restrictions. The odds ratio (OR), along with a 95% confidence interval (CI) of the effect sizes, are reported. Analyses including a subgroup analysis, a sensitivity analysis, and funnel plot analyses were conducted. Results: A total of 416 records were identified among the databases, and nine articles were entered into the meta-analysis. A significant relationship was found between the T allele of DEFB1 rs11362 polymorphism and DC susceptibility, and the T allele was related to an elevated risk of DC in children (OR = 1.225; 95%CI: 1.022, 1.469; p = 0.028; I2 = 0%). No other polymorphisms were associated with DC. All articles were of moderate quality. Egger's test in homozygous and dominant models demonstrated a significant publication bias for the association of DEFB1 rs1799946 polymorphism with DC risk. Conclusions: The results demonstrated that the T allele of DEFB1 rs11362 polymorphism had an elevated risk for DC in children. However, there were only few studies that evaluated this association.

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.

Genetic Variation in the MBL2 Gene Is Associated with Chlamydia trachomatis Infection and Host Humoral Response to Chlamydia trachomatis Infection.

This study aims to assess the potential association of MBL2 gene single nucleotide polymorphisms (SNPs) to Chlamydia trachomatis infection. We analysed a selected sample of 492 DNA and serum specimens from Dutch Caucasian women. Women were categorized into four groups of infection status based on the results of DNA and antibody tests for C. trachomatis: Ct-DNA+/IgG+, Ct-DNA+/IgG−, Ct-DNA−/IgG+, and Ct-DNA−/IgG−. We compared six MBL2 SNPs (−619G > C (H/L), −290G > C (Y/X), −66C > T (P/Q), +154C > T (A/D), +161A > G (A/B), and +170A > G (A/C)) and their respective haplotypes in relation to these different subgroups. The −619C (L) allele was less present within the Ct-DNA−/IgG+ group compared with the Ct-DNA−/IgG− group (OR = 0.49; 95% CI: 0.28−0.83), while the +170G (C) allele was observed more in the Ct-DNA+/IgG+ group as compared with the Ct-DNA−/IgG− group (OR = 2.4; 95% CI: 1.1−5.4). The HYA/HYA haplotype was more often present in the Ct-DNA−/IgG− group compared with the Ct-DNA+/IgG+ group (OR = 0.37; 95% CI: 0.16−0.87). The +170G (C) allele was associated with increased IgG production (p = 0.048) in C. trachomatis PCR-positive women. This study shows associations for MBL in immune reactions to C. trachomatis. We showed clear associations between MBL2 genotypes, haplotypes, and individuals' stages of C. trachomatis DNA and IgG positivity.

Mannose-binding lectin 2 gene polymorphisms and predisposition to allergic bronchial asthma in a western Romanian children population: an observational study.

OBJECTIVES: To analyse: (1) the associations between different mannose-binding lectin 2 (MBL2) genotypes and susceptibility to bronchial asthma (BA) in Romanian children; and (2) the correlations between several patient sociodemographic variables and MBL2 polymorphisms. METHODS: This prospective observational case-control study included paediatric patients with symptomatic BA and healthy controls. Participants were genotyped for two MBL2 single-nucleotide polymorphisms (SNPs): exon 1 codon 54 A/B variant rs1800450, and -550 promoter H/L variant rs11003125 (GenBank accession). Associations between MBL2 genotypes and susceptibility to BA were determined by calculated odds ratios, and Kendall Tau's correlations were used to investigate the associations between sociodemographic variables and SNPs. RESULTS: Among 59 patients with BA and 65 healthy controls, associations between MBL2 polymorphisms and susceptibility to BA were not found to be statistically significant. Statistically significant weak positive correlations were found between age at diagnosis and A/B genotype, and between the smoking status of biologically male and female parents. A statistically significant weak inverse association was found between male parent smoking status and family history of BA. CONCLUSION: These results may help guide future research into paediatric BA in Romania and Eastern Europe. Due to study limitations, the results require validation in future large-scale studies.

Impact of mannose-binding lectin gene polymorphism on lung functions among workers exposed to airborne Aspergillus in a wastewater treatment plant in Egypt.

In this study, the risk of Aspergillus (Asp.) positivity and its respiratory health impacts on wastewater treatment plant (WWTP) workers were studied. In addition, it identified the geno-susceptibility role of mannose-binding lectin 2 (MBL2) gene polymorphisms and the mannose-binding lectin (MBL) serum levels on the pulmonary functions of the Asp.-positive workers. Pulmonary function tests (PFTs) were performed for 89 workers from a selected WWTP, after exclusion of the smokers. Molecular identification of Asp. blood positivity was done by 18S rRNA sequencing. Determination of MBL2 gene polymorphism and estimation of MBL serum levels were done. PFTs revealed abnormalities in 49.2% of the workers. Asp. was positive in 42.5% of the workers with different species. Among the Asp.-positive workers, 6.5% of the workers were with obstructive PFTs, 12.9% with restriction, and 22.6% with combined PFT abnormalities. MBL2 genotyping showed that wild genotype AA was common (68.5%) among Asp.-positive workers compared to the other genotypes. This allele, whether homozygous or heterozygous, was significantly associated with decline in PFTs of the exposed workers. MBL serum levels were significantly lower in workers with obstructive, restrictive, and combined PFT abnormalities compared to those with normal PFTs, and in the workers with Asp.-positive species than the Asp.-negative workers. Moreover, it was significantly lower in workers with Asp. fumigatus compared to that in the workers with other Asp. species, and in the Asp.-positive workers with homozygous or heterozygous A allele compared to that in the Asp.-positive workers with homozygous B allele. Working in a WWTP can be associated with impaired PFTs due to exposure to airborne fungi. MBL2 genotyping showed that Asp.-positive workers with homozygous or heterozygous A allele were at risk to develop decline in their PFTs.

Mannose-binding lectin levels and MBL2 gene polymorphisms are associated with dengue infection in Brazilian children at the early ages.

BACKGROUND: The mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life. METHODS: We investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL. RESULTS: We found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases. CONCLUSIONS: MBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.

Association of mannose-binding lectin 2 (MBL2) and suppressor of cytokine signaling-1 (SOCS1) gene variants in children with febrile neutropenia.

INTRODUCTION: Febrile neutropenia (FEN) was reported in patients with solid malignancies at a rate of 5-10% and in patients with hematological malignancies at a rate of 20-25%. In our study, we aimed to investigate the effects of mannose-binding lectin 2 (MBL2) (rs1800450) and suppressor of cytokine signaling-1 (SOCS1) (rs33989964) gene variants on patients with FEN. METHODS: A total of 123 patients who applied to pediatric emergency department between December 2019-12/2020 included in the study. Thirteen patients were excluded from the study due to the inability to obtain DNA. Demographic-clinical features at initial diagnosis and genotype distributions were recorded. The control group consisted of volunteers with the same ethnicity, age and gender, no active infection, and no consanguinity. RESULTS: CA/CA genotype of SOCS1 was found to be significantly higher in the healthy control group (p = 0.028). AB/BB genotype of MBL2 was significantly higher in FEN patients with a MASCC score of high risk, AA genotype was found to be higher in patients with low risk (p = 0.001). While the rate of microbiologically documented infection (MDI) was significantly lower in patients with the AA genotype of MBL2, it was significantly higher in patients with AA/BB genotypes (p = 0.025). MDI rate in patients with the del/del genotype of SOCS1 was found to be significantly lower than in patients with CA/CA + CA/del genotypes (p = 0.026). CONCLUSIONS: In this study, it was revealed that low expression-related MBL2 genotypes were riskier for FEN and also, gene variants associated with high SOCS1 transcription were both protective against FEN and increased the rate of culture-negativity.

Functional Single-Nucleotide Polymorphisms in the MBL2 and TLR3 Genes Influence Disease Severity in Influenza A (H1N1)pdm09 Virus-Infected Patients from Maharashtra, India.

The clinical outcome in influenza A (H1N1)pdm09 virus-infected subjects is determined by several factors, including host genetics. In the present study, single-nucleotide polymorphisms (SNPs) in the IFITM, MBL2, TLR3, TLR8, DDX58, IFIH1, CD55, and FCGR2, genes were investigated in influenza A (H1N1)pdm09 virus-infected subjects to find out their association with disease severity. Influenza A (H1N1)pdm09 virus-infected subjects with severe disease (n = 86) and mild disease (n = 293) from western India were included in the study. The SNPs were investigated by PCR-based methods. The results revealed a higher frequency of TLR3 rs5743313 T/T genotype [odds ratio (OR) with 95% confidence interval (CI) 2.55 (1.08-6.04) p = 0.039] and TLR3 two-locus haplotype rs3775291-rs3775290 T-A [OR with 95% CI 7.94 (2.05-30.68)] in severe cases. Lower frequency of the mutant allele of MBL2 rs1800450 [OR with 95% CI 0.51 (0.27-0.87), p = 0.01] and TLR3 two-locus haplotype rs3775291-rs3775290 T-G [OR with 95% CI 0.48 (0.27-0.85)] was observed in severe cases compared with cases with mild disease. Higher frequency of TLR3 two-locus haplotype rs3775291-rs3775290 T-A was observed in severe cases [OR with 95% CI 7.9 (2.0-30.7)]. The allele and genotype frequencies of other SNPs were not different between the study categories. The results suggest that the functional SNPs in MBL2 and TLR3 are associated with severe disease in influenza A (H1N1)pdm09 virus-infected subjects.

Investigation of MBL2 and NOS3 functional gene variants in suspected COVID-19 PCR (-) patients.

For COVID-19 (Coronavirus Disease-2019) cases, detecting host-based factors that predispose to infection is a very important research area. In this study, the aim is to investigate the MBL2 and NOS3 gene polymorphisms in COVID-19 patients with lung involvement, whose first nasopharyngeal PCR results were negative. Seventy-nine patients diagnosed with COVID-19 between April-June 2020 who were admitted to a university hospital, and 100 healthy controls were included. In the first statistical analysis performed between PCR-positive, CT-negative and PCR-negative, CT-positive patients; the AB of MBL2 genotype was significantly higher in the first group (p = 0.049). The B allele was also significantly higher in the same subgroup (p = 0.001). The absence of the AB genotype was found to increase the risk of CT positivity by 6.9 times. The AB genotype of MBL2 was higher in healthy controls (p = 0.006). The absence of the AB genotype was found to increase the risk of CT positivity; also, it can be used for early detection and isolation of patients with typical lung involvement who had enough viral loads, but whose initial PCR results were negative.

MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19.

The COVID-19 pandemic represents one of the greatest challenges in modern medicine. The disease is characterized by a variable clinical phenotype, ranging from asymptomatic carriage to severe and/or critical disease, which bears poor prognosis and outcome because of the development of severe acute respiratory distress syndrome (SARS) requiring ICU hospitalization, multi-organ failure and death. Therefore, the determination of risk factors predisposing to disease phenotype is of outmost importance. The aim of our study was to evaluate which predisposing factors, including MBL2 genotyping, affected clinical phenotype in 264 COVID-19 patients. We demonstrated that older age along with underlying comorbidities, primarily obesity, chronic inflammatory disorders and diabetes mellitus, represent the most important risk factors related to hospitalization, the development of pneumonia and SARS. Moreover, we found that the presence of the MBL deficiency-causing B allele (rs1800450) was significantly associated with almost 2-fold increased risk for developing pneumonia and requiring hospitalization, suggesting its usage as a molecular predictor of severe disease in SARS-CoV-2 infected individuals.

Impact of MBL-2 coding region polymorphism on modulation of HAND and HIV-1 acquisition.

BACKGROUND: Mannose-binding lectin 2 (MBL2) gene has a significant role in the essential protective mechanism of the body. Variations reported in the genetic makeup of this gene influence the circulating MBL levels that could lead to the vulnerability to various viral infections including HIV. Hence, we assessed the MBL2 coding region (52A/D, 54A/B, and 57A/C) variations in HIV-associated neurocognitive disorders (HAND). METHOD: In this proposed study, 208 HIV seropositive individuals were included, 104 were on ART undergone for IHDS evaluation (44 HAND+60 without HAND), and 104 HIV seropositive individuals naïve to ART, and 130 unrelated HIV uninfected individuals. PCR-RFLP was used to genotype the MBL2 coding region polymorphism (52A/D, 54A/B and 57A/C). RESULTS: MBL-2 57AC genotype was associated with risk of HAND severity (OR = 4.69, P = 0.0009). MBL-2 57AC and 57C alleles were associated with susceptibility to HAND (OR = 3.14, P = 0.003). Furthermore, the MBL-2 57AC genotype and 57C allele were found to be significantly linked with the susceptibility to HIV disease severity. (OR = 6.34, P = 0.001; 16.82% vs. 3.46%, OR = 5.64, P = 0.001). Haplotype ACA was significantly linked with susceptibility to HAND and its severity (OR = 3.23, P = 0.004, 26.1%-8.1%, OR = 4.70, P = 0.0024), similarly, haplotype ACA was linked with the acquisition of HIV-1 (OR = 4.26, P = 0.005). MBL-2 57AC genotype in presence of tobacco showed a significantly higher risk for HIV disease severity (48.0% vs. 12.5%, OR = 7.00, P = 0.035). Alcohol-taking HIV seropositive individuals on ART showed a greater MBL-2 57AC genotype than with alcohol-taking naïve to ART (32.3% vs. 15.4%, OR = 2.75, P = 0.40). CONCLUSION: MBL-2 57AC genotype and haplotype ACA were associated with the modulation of HAND. Individuals with haplotype ACA were at higher risk of HIV-1 acquisition.

The role of Mannose-binding lectin in leprosy: A systematic review.

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.

Why does SARS-CoV-2 hit in different ways? Host genetic factors can influence the acquisition or the course of COVID-19.

The identification of high-risk factors for the infection by SARS-CoV-2 and the negative outcome of COVID-19 is crucial. The genetic background of the host might account for individual responses to SARS-CoV-2 infection besides age and comorbidities. A list of candidate polymorphisms is needed to drive targeted screens, given the existence of frequent polymorphisms in the general population. We carried out text mining in the scientific literature to draw up a list of genes referable to the term "SARS-CoV*". We looked for frequent mutations that are likely to affect protein function in these genes. Ten genes, mostly involved in innate immunity, and thirteen common variants were identified, for some of these the involvement in COVID-19 is supported by publicly available epidemiological data. We looked for available data on the population distribution of these variants and we demonstrated that the prevalence of five of them, Arg52Cys (rs5030737), Gly54Asp (rs1800450) and Gly57Glu (rs1800451) in MBL2, Ala59Thr (rs25680) in CD27, and Val197Met (rs12329760) in TMPRSS2, correlates with the number of cases and/or deaths of COVID-19 observed in different countries. The association of the TMPRSS2 variant provides epidemiological evidence of the usefulness of transmembrane protease serine 2 inhibitors for the cure of COVID-19. The identified genetic variants represent a basis for the design of a cost-effective assay for population screening of genetic risk factors in the COVID-19 pandemic.

A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations.

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project.