Mannose-binding Lectin Polymorphisms Research Articles

A possible association between low MBL/lectin pathway functionality and microbiota dysbiosis in endometriosis patients.

Endometriosis (EM) is a chronic inflammatory disorder with multifactorial etiologies (i.e., genetics and environmental factors, hormonal and immunological changes, and microbiome alterations). The complement system is one of the most frequently dysregulated pathways in EM. Mannose-binding lectin (MBL), a carbohydrate pattern recognition molecule, is the first described recognition subcomponent of the complement lectin pathway (LP). Here, we unveiled the interplay among MBL polymorphisms, plasma levels, LP functionality, and microbiota as potential contributors to EM pathogenesis. A cohort of 38 EM patients and 20 healthy controls was enrolled and the levels and functionality of the lectin pathway were assessed via ELISA assays. MBL genetic variants and the endometrial and vaginal microbiome were investigated and correlated. High MBL levels were related to the disease severity, although not accountable to the MBL2 genotype. MBL and MASP-2 were present in the uterine mucosa but appeared to have no function at the endometriotic lesion. EM patients with LP functional deficit displayed pathogenic bacterial species more frequently in the endometrial microbiome. Moreover, women affected by EM showed a higher frequency of rare gene variants in the estrogen pathway genes, potentially affecting MBL plasma levels. A lower functionality of LP in the uterine mucosa may contribute to an unbalanced bacterial environment that could activate endometrial cells. Not only the genotype and the inflammatory condition, but also the estrogen pathway can cause altered MBL levels, thus contributing to changes in the LP functionality.

Association of MBL2 gene polymorphisms and MBL levels with dilated cardiomyopathy in a Chinese Han population

BackgroundIt has been reported that Mannose-binding lectin 2 (MBL2) gene polymorphisms and expression levels are related to dilated cardiomyopathy (DCM). This study aimed to investigate the potential association between MBL2 gene polymorphisms and the pathogenesis of DCM.MethodsFive single nucleotide polymorphisms (SNPs) of the MBL2 gene were genotyped in 440 DCM patients and 532 controls in Southwest China. A luciferase reporter assay was used to detect the transcriptional activity the different genotypes. MBL serum levels, left ventricle ejection fraction (LVEF) and lower left ventricular end-diastolic diameter (LVEDD) were measured.ResultsThe rs11003125 C allele increased the transcriptional activity of the MBL2 promoter compared with the rs11003125 G allele. The rs11003125 CC carriers had higher MBL serum levels, LVEF and LVEDD than the rs11003125 CG and GG carriers.ConclusionsOur study first revealed that MBL2 polymorphisms and serum MBL levels were associated with DCM. Allele C in rs11003125 of MBL2 may upregulate the expression levels of MBL. High serum MBL levels may be a protective factor in DCM pathogenesis.

Single nucleotide polymorphism, haplotypes and genotypes of Mannose-binding lectin (MBL1) gene and their association with clinical mastitis in Murrah buffalo

The Mannose-binding lectin (MBL1) gene is an important component of immune response system. It plays vital role in activation of the complement system and act as chief defense molecule of host cell to provide protection against various diseases. In the recent study, six novel single nucleotide polymorphisms (SNPs), at 2689G>C, 2751A>G, 4822T>C, 4853A>G, 4855T>C, and 4978T>C resulted in 2 non synonymous type of change at 4853A>G, 4855T>C resulting in one amino acid substitution Ser150Gly of MBL1 protein and their association with clinical mastitis were investigated in two hundred (200) Murrah buffaloes. These SNPs in MBL1 were genotyped by using the polymerase chain reaction (PCR) and Deoxyribose nucleic acid (DNA) sequencing methods in order to reveal the association with clinical mastitis. SHEsis software tool was used for construction of haplotypes and Linkage disequilibrium analysis. Twenty one (21) haplotypes were constructed. Allelic association analysis showed that C allele of 2689 G>C, A allele of 2751 A>G, C allele of 4822 T>C, A allele of 4853 A>G, C allele of 4855 T>C, and C allele of 4978 T>C had significant association with increased risk of clinical mastitis in Murrah buffaloes (P<0.05). Murrah buffaloes with CG genotype of 2689 G>C, AG or GG genotype of 2751 A>G, CC genotype of 4822T>C, AG or GG genotype of 4853 A>G, TC or CC genotype of 4855 T>C and CC genotype of 4978 T>C loci had significantly lower incidence of clinical mastitis compared to their counter genotypes. Haplotype association analysis showed that Hap21 (TATTGA) was found significantly related to higher risk of clinical mastitis (P<0.05). Hap14 (TGTTGG) and Hap5 (CGCCCA) were found significantly associated with lower risk of clinical mastitis in Murrah buffalo (P<0.05).

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and theirpolymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotypeDD was found to be associated with COVID-19 cases in the urban population of Patna city.

Role of Mannose-binding Lectin and Association with Microbial Sensitization in a Cohort of Patients with Atopic Dermatitis

Atopic dermatitis is a relapsing inflammatory skin condition, in which bacteria, fungi and viruses may colonize the skin and aggravate the condition. Mannose-binding lectin is part of the innate immune system. Polymorphism in the mannose-binding lectin gene can result in deficiency of mannose-binding lectin, which may affect defence against microbes. The aim of this study was to investigate whether polymorphisms in the mannose-binding lectin gene affect the extent of sensitization to common skin microbes, the skin barrier function, or the severity of the disease in a cohort of patients with atopic dermatitis. Genetic testing of mannose-binding lectin polymorphism was performed in 60 patients with atopic dermatitis. The disease severity, skin barrier function, and serum levels of specific immunoglobulin E against skin microbes were measured. In patients with low mannose-binding lectin genotype (group 1) 6 of 8 (75%) were sensitized to Candida albicans, compared to 14 of 22 (63.6%) patients with intermediate mannose-binding genotype (group 2) and 10 of 30 (33.3%) patients with high mannose-binding genotype (group 3). Group 1 (low mannose-binding lectin) was more likely to be sensitized to Candida albicans compared with group 3 (high mannose-binding lectin) (odds ratio 6.34, p-value 0.045). In this cohort of patients with atopic dermatitis, mannose-binding lectin deficiency was associated with increased sensitization to Candida albicans.

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.

Gene polymorphisms and serum levels of mannose-binding lectin in Czech patients with recurrent aphthous stomatitis: A case-control study.

Recurrent aphthous stomatitis is one of the most prevalent oral mucosal immunological diseases. A recent case-control study in the Egyptian population suggested that single nucleotide polymorphism Gly54Asp (rs1800450) of the mannose-binding lectin 2 gene might affect the mannose-binding lectin serum level and recurrent aphthous stomatitis development. The aim of this study was to determine the distribution of six functional mannose-binding lectin 2 gene polymorphisms and analyse their role in recurrent aphthous stomatitis susceptibility in the Czech population. The study included 227 subjects; 137 healthy people and 90 patients with recurrent aphthous stomatitis. Six mannose-binding lectin 2 gene polymorphisms (rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, rs1800451) were analysed by the SNaPshot assay method, mannose-binding lectin serum levels were determined by enzyme-linked immunosorbent assay (ELISA) method in a subgroup of subjects (N=87). No significant differences in mean of mannose-binding lectin serum levels between healthy controls and patients with recurrent aphthous stomatitis were observed (383 ng/ml ± 249 standard deviation (SD) vs. 316 ng/ml ± 177 SD in remission phase vs. 343 ng/ml ± 254 SD in active phase; p > 0.05), also the allele and genotype frequencies of the studied mannose-binding lectin 2 polymorphisms did not differ significantly between the two groups (p > 0.05, odds ratio (OR): 0.75-1.23). Moreover, the distribution of mannose-binding lectin 2 haplotypes and haplogenotypes was similar in the healthy subjects and patients with recurrent aphthous stomatitis (p > 0.05, OR: 0.75-1.23). This study did not confirm the previously reported association of the mannose-binding lectin 2 Gly54Asp gene variant and low mannose-binding lectin serum level as the risk factors for susceptibility to recurrent aphthous stomatitis. In addition, no significant relationships between mannose-binding lectin 2 functional haplotypes or haplogenotypes and recurrent aphthous stomatitis were observed.

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

ObjectivesTo 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.MethodsThis 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.ResultsAmong 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.ConclusionThese 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.

Influence of the presence of mannose-binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta-analysis

BackgroundLeishmaniasis is caused by an intracellular protozoan of the Leishmania genus. Mannose-binding lectin (MBL) is a serum complement protein and recognizes lipoprotein antigens in protozoa and the bacterial plasma membrane. Nucleotide variants in the promoter region and exon 1 of the MBL gene can influence its expression or change its molecular structure. ObjectiveTo evaluate, through a systematic review, case-control studies of the genetic association of variants in the MBL2 gene and the risk of developing leishmaniasis. MethodsThis review carried out a search in PubMed, Science Direct, Cochrane Library, Scopus and Lilacs databases for case-control publications with six polymorphisms in the mannose-binding Lectin gene. The following strategy was used: P = Patients at risk of leishmaniasis; I = Presence of polymorphisms; C = Absence of polymorphisms; O = Occurrence of leishmaniasis. Four case/control studies consisting of 791 patients with leishmaniasis and 967 healthy subjects (Control) are included in this meta-analysis. The association of variants in the mannose-binding Lectin gene and leishmaniasis under the allelic genetic model, -550 (Hvs. L), -221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) and A/O genotype (A vs. O) was evaluated. International Prospective Register of Systematic Reviews (PROSPERO): CRD42020201755. ResultsThe meta-analysis results for any allelic genetic model showed no significant association for the variants within the promoter, the untranslated region, and exon 1, as well as for the wild-type A allele and mutant allele O with leishmaniasis. Study limitationsCaution should be exercised when interpreting these results, as they are based on a few studies, which show divergent results when analyzed separately. ConclusionsThis meta-analysis showed a non-significant association between the rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451 polymorphisms of the Mannose-binding Lectin gene and leishmaniasis in any allelic and heterogeneous evaluation.

Mannose-binding lectin gene polymorphism and the susceptibility of sepsis: A meta-analysis

Objective To assess the association between the Mannose-binding lectin (MBL) gene polymorphism and the susceptibility to sepsis using a meta-analysis. Methods The publications were searched on PubMed, Embase, and Web of Science databases up to December 1, 2019 for relevant literature. Results A total of 32 studies (21 adult and 11 pediatric studies) were selected for analysis. Overall, in the three models of MBL +54 A/B gene polymorphisms, namely the dominant model BB + AB vs. AA ( p = 0.03), the recessive model BB vs. AB + AA ( p < 0.00001), and the allele model B vs. A ( p = 0.04), MBL +54 A/B was significantly related to the risk of sepsis. In the adult group, the MBL A/O gene polymorphism was associated with the risk of sepsis in the dominant model AO + OO vs. AA ( p = 0.006) as well as in the allele model O vs. A ( p = 0.04). The MBL +54 A/B gene polymorphism was significantly related to the risk of sepsis in the recessive model and, therefore, may increase the risk of sepsis. In the pediatric group, no polymorphic loci were significantly associated with sepsis in any of the three models. The results of the publication bias test demonstrated no publication bias in an unadjusted estimate of the relationship between MBL A/O and −211Y/X gene polymorphism and sepsis. Conclusions The polymorphisms of MBL that are related to the occurrence of sepsis are primarily A/O and +54 A/B, while −221Y/X and −550H/L have no clear relationship with the susceptibility of sepsis in various age groups or different models.

Importance of mannose-binding lectin2 polymorphism (rs1800450) in infections in children

Purpose Mannose-binding lectin (MBL) is a serine protease belonging to the collectins and an important factor in the inherited immune system. We aimed to reveal the distribution of different MBL2 genotypes in patients diagnosed with acute bronchiolitis and pneumonia. Material and methods A total of 147 patients who applied to Paediatric Emergency between 01.12.2019 and 31.12.2020 were included in the study. Patients were divided into two subgroups: Bronchiolitis and pneumonia. Results AA genotype was found to be significantly higher in healthy controls (p = 0.039). In the pneumonia group, both AB/BB genotype was significantly higher compared to healthy controls (p = 0.001). While the AA genotype was more common in patients with acute bronchiolitis, AB/BB genotypes were more common in the pneumonia group (p = 0.001). The presence of fever, crepitation, tachypnoea, pathological x-ray finding, and high leukocyte count are significantly more common in patients with AA genotype, while more than 3 days of follow-up duration and severe clinical picture were more common in patients with AB/BB genotypes (p < 0.05, for all). Conclusions Genotypes with low MBL expression were significantly more common in patients with pneumonia and severe infection. All these results reveal the importance of MBL polymorphisms and their expression in infections.

Investigation of inflammation related gene polymorphism of the mannose-binding lectin 2 in schizophrenia and bipolar disorder.

Objectives:To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).Methods:One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.Results:The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).Conclusion:The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

Effect of Clinical, Biochemical, and Genetic Variations on Medical Management in Filarial Chyluria: A Prospective Study at a Tertiary Care Centre in North India.

ObjectiveTo analyze the effect of clinical, biochemical factors, and Mannose Binding Lectin 2 (MBL2) gene variations on medical management in filarial chyluria (FC) patients.Material and methodsWe conducted a study between March 2013 and April 2016. MBL2polymorphisms were genotyped in confirmed 101 medically-treated cases of FC. Demographic, clinical, and biochemical variables were compared between remission and failure groups. Genotyping of MBL2 codon 54 and promoter -221 were undertaken by polymerase chain reaction. Genotype frequencies were compared with clinical and biochemical variables and medical treatment outcomes (remission/failure). The association between genotypes and treatment response was estimated by OR and 95% CI and generated by the chi-square test.ResultsThe mean age was 36.9±10.28-years and the male-female ratio was 3:1.2. Sixty-six patients had remission (Group-A) while 35 had recurrence (Group-B) at a mean follow-up of 21 months. The success rate for medical therapy was 65.35%. There was no statistical difference observed in the demographic profile of the two groups. On multivariate analysis, patients in Group-B had a higher grade of chyluria (p=0.005), had experienced greater number of disease attacks in the past (p=0.022), and had higher urinary triglyceride levels (TG) (p<0.001) as compared to Group-A patients. A significant association of MBL2 codon 54 genotypes was observed with the recurrent presentation of chyluria (p=0.044), grade of chyluria (p=0.028), and urinary TGs (p=0.001). However, genotype distribution at -221 did not show association with clinical and biochemical parameters of FC patients. The distribution of genotypes at codon 54 differed significantly between remission and failure/recurrence group; the variant genotype BB was significantly higher in the recurrence or failure group (OR:6.00; 95%CI, 1.00-35.91; p=0.050). However, frequencies of variant genotype YX and recessive group YX+XX of MBL2 -221 promoter was higher in remission group (OR:2.97;95%CI, 1.23-7.13; p=0.018 and OR:2.76; 95%CI, 1.80-6.50; p=0.020), respectively, showing that genetic variant may be associated with response to medical therapy.ConclusionHigher grade of chyluria, a higher number of disease attacks in the past, and higher urinary TGs levels were clinical predictors of poor response to medical treatment. Our results showed that the variants of MBL2 genes have an impact on treatment outcomes in FC patients. These observations may be limited by sample size.

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.

Effect of mannose-binding lectin gene polymorphisms on the risk of rheumatoid arthritis: Evidence from a meta-analysis.

BackgroundThe effect of mannose‐binding lectin (MBL) gene polymorphisms on susceptibility of rheumatoid arthritis (RA) were evaluated in ethnically different populations, whereas the results were always inconsistent.Materials and methodsFourteen articles involving 36 datasets were recruited to evaluate the association between MBL gene polymorphisms and rheumatoid arthritis in a meta‐analysis. The random or fixed effect models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).ResultsStratified analysis by ethnicities was conducted and the result revealed that rs1800450 (T vs C, OR = 1.32, 95% CI: 1.04‐1.67, P < .05) and MBL‐A/O (T vs C, OR = 1.20, 95% CI: 1.08‐1.34, P < .001) were strongly associated with RA in Brazilian populations. In addition, the significant relationship between rs11003125 (T vs C, OR = 1.16, 95% CI: 1.06‐1.26, P < .05) with RA were also observed in East Asian populations. Meanwhile, the inverse associations between rs5030737 with RA in East Asians and rs1800450 with RA in Indians were acquired. However, no association between any MBL polymorphism with RA susceptibility was confirmed in Caucasians.ConclusionsThe structural polymorphisms in exon 1 of MBL gene may significantly contribute to susceptibility and development of RA in Brazilian and Indian populations, whereas the functional polymorphisms in the promoter region were more likely to associate with RA in East Asians.

Local and Systemic Concentrations of Pattern Recognition Receptors of the Lectin Pathway of Complement in a Cohort of Patients With Interstitial Lung Diseases.

BackgroundThe role of the lectin pathway of complement in the pathogenesis of interstitial lung diseases (ILDs) is largely unknown. Pattern recognition receptors (PRR) of the lectin pathway are involved in the clearance of apoptotic cells either via activation of the complement system or as direct opsonins. As recent findings suggest a role of apoptosis in the development of pulmonary fibrosis, the influence of plasma lectins has lately been considered in various ILDs, but data on local concentrations in the lungs are lacking. This study investigated the role of mannose-binding lectin (MBL), ficolin-2 and ficolin-3 in ILD patients with a focus on idiopathic pulmonary fibrosis (IPF) and sarcoidosis.MethodsA case control study was conducted involving 80 patients with different forms of ILD as well as 40 control patients undergoing routine flexible bronchoscopy with bronchoalveolar lavage (BAL). Plasma and BAL fluid (BALF) levels of MBL, ficolin-2 and ficolin-3 as well as complement split products C4d and C5a (only in BALF) were measured by enzyme-linked immunosorbent assays. Eight single-nucleotide polymorphisms (SNPs) of MBL and ficolin-2 were determined by genotyping and tested for their association with ILDs.ResultsWe included 35, 35, 10, and 40 patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), other ILD, and a control group, respectively. BALF but not plasma levels of the three PRR were significantly elevated in sarcoidosis patients compared to a control group without ILD (MBL: median 66.8 vs. 24.6 ng/ml, p = 0.02, ficolin-2: 140 vs. 58.8 ng/ml, p = 0.01, ficolin-3: 2523 vs. 1180 ng/ml, p = 0.02), whereas the frequency of the investigated SNPs was similar. In line, complement split products were markedly elevated in BALF of sarcoidosis patients (C4d, median 97.4 vs. 0 ng/ml, p = 0.10; C5a, 23.9 vs. 9.1 ng/ml, p = 0.01). There was a weak positive correlation of BALF ficolin-3 with serum neopterin, a marker of sarcoidosis activity. In IPF patients, we observed numerically higher MBL plasma and BALF levels (plasma, median 1511 vs. 879 ng/ml, p = 0.44; BALF, 37.5 vs. 24.6 ng/ml, p = 0.7) as well as lower ficolin-2 plasma levels (plasma 1111 vs. 1647 ng/ml, p = 0.11). Ficolin-2 plasma levels were inversely correlated with the forced vital capacity (r = 0.55, p = 0.1).ConclusionThis is the first study to simultaneously assess systemic and local lectin pathway protein levels in ILD patients. Our data suggest an involvement of PRR of the lectin pathway in the pathogenesis of sarcoidosis given the significantly higher BALF levels compared to a control group. Additional analyses in a larger patient cohort are required to confirm or refute a potential effect of local and/or systemic ficolin-2 levels in IPF patients.

Association between polymorphisms in mannose-binding lectin 2 gene with pulmonary tuberculosis susceptibility

BackgroundMannose-binding lectin (MBL2) is considered to play a role in the human innate immune response to tuberculosis (TB) infections, and 4 common single nucleotide polymorphisms (SNPs) may be associated with pulmonary tuberculosis (PTB) risk. To examine these potential associations, we performed a comprehensive analysis to assess the relationships between MBL2 polymorphisms and PTB.MethodsThe PubMed, Embase, and SinoMed databases were searched for articles published prior to June 13, 2019. Odds ratios with 95% confidence intervals were calculated to evaluate the strength of the relationships.ResultsThere were 37 case-control studies examining the effects of the four SNPs in MBL2 on PTB. A positive association between rs11003125 and PTB risk was observed in the hospital-based subgroup. Moreover, for the combined polymorphism and PTB risk, positive associations were detected not only in the total population but also in those with Asian origins across all source of control subgroups. No associations were found for rs7096206 or rs7095891.ConclusionsOur current study indicated that several SNPs in MBL2 may be associated with susceptibility to PTB.

Association of MIF and MBL2 gene polymorphisms with attempted suicide in patients diagnosed with schizophrenia or bipolar disorder

The aim of this study to investigate the genetic polymorphisms in macrophage inhibitory factor (MIF) and mannose-binding lectin 2 (MBL2) gene in schizophrenia (SCZ) or bipolar disorder (BD) patients with attempted suicide by comparing with a non-attempted SCZ or BD patients and healthy controls. A sample of 108 patients with SCZ, 100 patients with BD and 100 healthy volunteers were included in the study. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The patients were evaluated by data forms that included sociodemographic, suicidal behavior and symptom severity information. PCR-RFLP was used to determine MIF and MBL2 gene polymorphisms from DNA material. Our results demonstrated that the distributions of MBL2 genotype (AA, AB, BB), combined genotype (AA, AB/BB) and the allele frequencies (A, B) of attempted suicide patients in SCZ were significantly different from the non-attempted SCZ patients. The distributions of the MBL2 genotype of attempted suicide patients in SCZ were significantly different from the control group. The distributions of MIF genotype (GG, GC, CC), combined genotype (GG, GC/CC) and the allele frequencies (G, C) of attempted suicide patients in BD were significantly different from the non-attempted BD patients or control group. In summary MBL2 gene polymorphism may be associated with attempted suicide in SCZ and MIF gene polymorphism might be associated with attempted suicide in BD. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of these polymorphisms in SCZ or BD.

The Occurrence of High Frequencies of MBL2 polymorphisms in the Xhosa ethnic group of South Africa

Polymorphic changes in a given population give rise to genetic variations. These variations account for differences found within a population. One of the most abundant and common genetic variant that occur in the population is the Single Nucleotide Polymorphisms which are point mutations in genes. The study assessed the frequency of single nucleotide polymorphisms in mannose binding lectin ( MBL2 ) gene namely rs8191996, rs1838065, rs8179079 and rs1800450 in 366 adult individuals drawn from Xhosa ethnic group of South Africa. The polymorphisms showed high frequencies in its occurrence which was 0.71, 0.42, 0.71 and 0.73 for rs8191996, rs1838065, rs1800450 and rs8179079 respectively. Additionally, the genotype distribution of these polymorphisms showed a predominance of homozygotes over heterozygotes and were in accordance with Hardy-Weinberg principle. The high frequencies of the MBL2 polymorphisms under study in this population suggest that there is a high incidence of single gene mutations in Xhosa ethnic group which could make the population vulnerable to infection. DOI: 10.7176/JBAH/10-6-04 Publication date: March 31 st 2020

THE ASSOCIATION BETWEEN GENETIC POLYMORPHISMS OF TOLL-LIKE RECEPTORS AND MANNOSE-BINDING LECTIN AND ACTIVE TUBERCULOSIS IN HIV-INFECTED PATIENTS

Objectives: to analyze the association between genetic polymorphisms of Toll-like receptors (TLR) and mannose-binding lectin (MBL) and active tuberculosis in HIV-infected patients to consider the possibility of using genetic markers as a way to personalize the chemoprophylaxis of tuberculosis in this category of patients. Materials and methods : The study enrolled 171 patients (85 HIV-infected, 86 HIV/TB co-infected patients). Single nucleotide polymorphisms (SNP) in the TLR4 (rs4986790), TLR2 (rs5743708) and MBL2 (rs5030737, rs1800450, rs1800451) were genotyped by real-time PCR and pyrosequencing. Data about epidemiological risk factors were obtained from epidemiological anamnesis. Immune status was assessed by the level of CD4+ T-cells count. Results : Statistically significant association with active tuberculosis was identified for the genotype AG of TLR4, rs4986790 (OR=5.2; 95% CI: 1,8–14,6, p=0,002). Multivariate analysis shows that close contact with TB patientand status of ex-prisoner increased the risk of active tuberculosis 5,2 times (OR=5,2; 95% CI: 1,4–18,5, p=0,012 and OR=5,2; 95% CI: 1,5–17,7, p=0,009, respectively); CD4+ T-cell count more than 200 cells/mm 3 exerted protective effect and reduced the risk of developing TB 5 times (OR=0,2; 95% CI: 0,1–0,5, p=0,001). The genotype AG of TLR4, rs4986790 increased the risk of active tuberculosis 3,7 times (OR=3,7; 95% CI: 1,1–13,1, p=0,046). Conclusion . The G allele of TLR4, rs4986790 can be considered as an independent risk factor for active tuberculosis in HIV-infected individuals. These results need to be confirmed by further investigations on large samples.