Mannose-binding Lectin Genotype Research Articles

115 The mannose-binding lectin (MBL) in MIS-C: relationship between MBL genotype, levels, and functional activity against SARS-CoV-2

115 The mannose-binding lectin (MBL) in MIS-C: relationship between MBL genotype, levels, and functional activity against SARS-CoV-2

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.

Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality

Mannose-binding lectin (MBL) is crucial in first-line immune defenses. There are still many unknown factors regarding the mechanisms causing variability in the clinical course of coronavirus disease 2019 (COVID-19). In Japan, there have been few reports to date regarding the association between MBL and COVID-19. It has been demonstrated that the MBL2 gene B variant at codon 54 (rs1800450) is associated with variabilities in the clinical course of COVID-19. We aimed to investigate how the level of serum MBL and the codon 54 variant of MBL (rs1800450) affect the disease severity of COVID-19. A total of 59 patients from the fourth wave and 49 patients from the fifth wave in Japan were analyzed based on serum MBL levels using ELISA and the genotype of MBL2 codon 54 using PCR reaction. There was no significant association between serum MBL levels and age. MBL2 genotype was independent of age, there was no significant difference in different COVID-19 severities, MBL genotypes, and serum MBL levels. Binary logistic regression analysis to identify predisposing factors for severe COVID-19 symptoms demonstrated that patients with the BB genotype had a higher risk of death from COVID-19. Our results quantitatively demonstrated that the BB genotype might be a factor associated with death from COVID-19.

Mannose-binding lectin genotype is associated with respiratory disease in young children: A multicenter cohort study.

Mannose-binding lectin (MBL) is an important component of the innate immune system. Polymorphisms in the MBL2 gene and promoter region are directly associated with MBL-deficiency. We sought to determine the association between MBL genotype on the frequency of common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood. MBL2 gene variants were analyzed in newborns recruited to the GO-CHILD multicenter prospective cohort study. Follow-up for respiratory infection and atopy diagnoses and symptoms, healthcare utilization, and medication prescription were conducted by postal questionnaires at 12 and 24 months. Genotyping and follow-up were completed in 1004 children. Genotypes associated with MBL-deficiency were associated with an increased risk of bronchiolitis (relative risk [RR] 1.95, 95% confidence interval [CI] 1.33-2.85) and pneumonia (RR 2.46, 95%CI 1.16-5.22). MBL-deficient genotypes were associated with an increased risk of wheeze with shortness of breath episodes (RR 1.22, 95%CI 1.04-1.43), emergency department attendance (RR 1.90 95%CI 1.13-3.19), and hospital admission (RR 2.01, 95%CI 1.04-3.89) for wheeze. MBL-deficient genotypes were associated with a reduced risk of developing atopic dermatitis (RR 0.72, 95%CI 0.53-0.98). The positive association between MBL-deficient genotypes and bronchiolitis and pneumonia, as well as a severe wheeze phenotype in some young children, supports the hypothesis that MBL is an important component of innate immunity in the vulnerable period before the maturation of the adaptive immune system. Identification of disease-modifying genotypes may help target preventative strategies in high-risk infants.

Comparative profiling of the resistance of different genotypes of mannose-binding lectin to Mycoplasma pneumoniae infection in Chinese Merino sheep based on high-throughput sequencing technology

Mannose-binding lectin (MBL) glycoproteins in blood can selectively recognise lectins on the surface of bacteria, and play an important role in natural immunity. Micro RNAs (miRNAs) are key molecules that regulate gene expression at the post-transcriptional level in vivo, and their pathways are specific and effective. Previous studies indicate that small RNAs such as miRNAs perform regulatory roles in immunology. Herein, we investigated differential expression of miRNAs during MBL protein immunotherapy in sheep following treatment with different MBL genotypes (resistant and susceptible), and identified miRNAs linked to different target genes and pathways. RNA was extracted from liver tissue of resistant and susceptible sheep, miRNAs were identified by high-throughput sequencing, and differentially expressed miRNAs were analysed by SOAP to predict target genes and biological pathways. Results: Some miRNAs (oar-mir-143, oar-mir-10b, oar-mir-382, oar-mir-432 and oar-mir-379) were up-regulated, while others were down-regulated. GPATCH3 and DNAJC5 were predicted target genes of oar-mir-379, DMRT1 and GATA4 were linked to oar-mir-382, and oar-mir-432 was associated with STAT2, DMRT1 and ATG16L1. Identification of miRNAs differentially expressed in resistant and susceptible sheep may expand our understanding of miRNAs in immune regulation, and the role of MBL in innate immunity.

The Role of Mannose-binding Lectin in Infectious Complications of Pediatric Hemato-Oncologic Diseases.

The complement system is essential for protection against infections in oncologic patients because of the chemotherapy-induced immunosuppression. One of the key elements in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. The objective of our study was to find an association between polymorphisms resulting in low MBL level and activation of the MBL-MASP2 complex. Also, we aimed at finding a connection between these abnormalities and the frequency and severity of febrile neutropenic episodes in children suffering from hemato-oncologic diseases. Ninety-seven patients had been enrolled and followed from the beginning of the therapy for 8 months, and several characteristics of febrile neutropenic episodes were recorded. Genotypes of 4 MBL2 polymorphisms (-221C/G, R52C, G54D, G57E) were determined by real-time polymerase chain reaction. Activation of the MBL-MASP2 complex was evaluated by enzyme-linked immunosorbent assay at the time of diagnosis and during an infection. The number of febrile neutropenic episodes was lower, and the time until the first episode was longer in patients with normal MBL level than in patients with low MBL level coding genotypes. The MBL-MASP2 complex activation level correlated with the MBL genotype and decreased significantly during infections in patients with low MBL level. Our results suggest that infections after immunosuppression therapy in children suffering from hemato-oncologic diseases are associated with the MBL2 genotype. Our results may contribute to the estimation of risk for infections in the future, which may modify therapeutic options for individuals.

Mannose Binding Lectin, S100 B Protein, and Brain Injuries in Neonates With Perinatal Asphyxia.

Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Complement activation and neuroinflammation worsen brain damage after a systemic ischemia/reperfusion insult. The increase of mannose binding lectin (MBL) during asphyxia may contribute to the brain damage, via activation of the complement lectin pathway. The possible role of MBL2 gene variants in influencing the severity of post-asphyxia brain injuries is still unexplored. This retrospective study included 53 asphyxiated neonates: 42 underwent therapeutic hypothermia (TH) and 11 did not because they were admitted to the NICU later than 6 h after the hypoxic insult. Blood samples from TH-treated and untreated patients were genotyped for MBL2 gene variants, and biomarker plasma levels (MBL and S100 B protein) were measured at different time points: during hypothermia, during rewarming, and at 7–10 days of life. The timing of blood sampling, except for the T1 sample, was the same in untreated infants. Highest (peak) levels of MBL and MBL2 genotypes were correlated to neuroimaging brain damage or death and long-term neurodevelopmental delay. MBL2 wild-type genotype was associated with the highest MBL levels and worst brain damage on MRI (p = 0.046) at 7–10 days after hypoxia. MBL increased in both groups and S100B decreased, slightly more in treated than in untreated neonates. The progressive increase of MBL (p = 0.08) and to be untreated with TH (p = 0.08) increased the risk of brain damage or death at 7–10 days of life, without affecting neurodevelopmental outcomes at 1 year. The effect of TH on MBL plasma profiles is uncertain.

Impact of mannose-binding lectin 2 gene polymorphisms on disease severity in noncystic fibrosis bronchiectasis in children.

Mannose-binding lectin (MBL) is a complement protein involved in the innate immune system, and is associated with some chronic respiratory diseases including noncystic fibrosis (non-CF) bronchiectasis in adults. The aim of this study was to investigate the frequency of MBL2 gene polymorphisms in children with non-CF bronchiectasis, and the effect of MBL deficiency on disease severity. Fifty children with non-CF bronchiectasis (bronchiectasis group) and 50 healthy controls (control group) were included. The demographic findings, number of acute pulmonary exacerbations in the previous year, airway cultures, pulmonary function tests, and radiologic scores of the bronchiectasis group were recorded. DNA extraction was performed in both groups and MBL2 gene polymorphisms in codons 52, 54, 57 in exon 1 and H/L, Y/X in the promoter region were studied using real-time polymerase chain reaction. Haplotypes were made by genotypes, and MBL serum expression was classified according to the genotypes in the literature. The bronchiectasis group consisted of 23 (46%) patients with primary ciliary dyskinesia, 5 (10%) with primary immunodeficiency diseases, and 22 (44%) with idiopathic bronchiectasis. There were no statistically significant differences between the bronchiectasis and control groups in terms of allele and genotype frequencies of polymorphisms in codons 52, 54, 57 in exon 1 and promoter H/L. However, the YX heterozygote genotype was more frequent in the control group (82%) compared with the bronchiectasis group (50%) (P = .002). The frequency of patients with intermediate serum MBL expression genotype was higher in the bronchiectasis group (20%) than in the control group (0%) (P = .001). In the bronchiectasis group, there were no significant differences in growth, annual pulmonary exacerbation rates in the last year, pulmonary function tests, radiologic scores, and microbiologic findings between low, intermediate, and high-expressing genotypes. In children with non-CF bronchiectasis, MBL genotype was different from healthy controls. MBL deficiency associated only with MBL genotype was not related to disease severity in this group of patients.

The impact of mannose-binding lectin polymorphisms on lung function in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a congenital lung disease that leads to recurrent and chronic lung infection. The resulting inflammation causes lung damage and declines in lung function. Mannose-binding lectin (MBL) is a first line host defense protein of importance for the innate immunity. Polymorphisms in the MBL gene named MBL2 result in unstable and low functional levels MBL proteins. MBL insufficiency is linked to an increased risk of lung infection and to declines in lung function in patients with cystic fibrosis. We investigated whether there is a similar link in patients with PCD. This retrospective longitudinal study included 85 patients with PCD. Diagnostics and age at diagnosis were recorded, complete spirometry data starting at diagnosis, and Pseudomonas aeruginosa infection status over the last 2 years were collected, and the patients were grouped according to MBL2 genotype status (MBL2-sufficient or MBL2-deficient). MBL-deficient patients were diagnosed almost 3 years earlier than MBL-sufficient patients (median 6.1 vs 8.9 years, P < 0.05). There were no differences in the first measured spirometry values, but MBL-deficient patients showed greater declines in forced expiratory volume in one sec (FEV1 ) than patients with MBL sufficiency (z-score: -0.049 per year [95% CI, -0.075; -0.021] vs -0.009 per year [95% CI, -0.033; 0.015]; P = 0.023). No differences were found in forced vital capacity (FVC), FEV1 /FVC, or infection status. MBL-deficiency, which is associated with MBL2 mutations, was associated with a lower age at diagnosis and with steeper declines in FEV1 in patients with PCD. This suggests that the MBL genotype might be a disease modifier in PCD.

Mannose binding lectin and prediction of risk for chemotherapy induced febrile neutropenia in patients with a solid tumor

Mannose-binding lectin (MBL) - deficient patients who undergo chemotherapy for a solid tumor might have an increased risk developing febrile neutropenia (FN). We investigated in a prospective cohort study relations between MBL-serum levels and polymorphisms in MBL promotor genotypes (−550H/L and −221X/Y) on incidence and severity of FN. Risk of FN was 17.9% in MBL-deficient and 22.5% in MBL-sufficient patients (RR = 0.796, p = 0.45). Median MBL serum levels at baseline were respectively 1.39 µg/mL and 1.09 µg/mL (p = 0.92) in patients with and without FN. In conclusion, serum MBL and MBL genotypes (−550H/L and −221X/Y) do not determine the risk for developing FN.

Use of Mannose-Binding Lectin Gene Polymorphisms and the Serum MBL Level for the Early Detection of Neonatal Sepsis.

Background Mannose-binding lectin (MBL) is a component of innate immunity and is particularly important in neonates, in whom adaptive immunity has not yet completely developed. MBL deficiency and MBL2 gene polymorphisms are associated with an opsonization defect and have been associated with neonatal sepsis. Aim The aim of our study was to assess serum MBL levels and genotype MBL2 genes to determine whether they can serve as markers for predicting neonatal sepsis in neonatal intensive care units. Patients and Methods A case-control study was conducted with 114 neonates classified into two groups: the septic group included 64 neonates (41 preterm and 23 full-term infants), and the non-septic control group included 50 neonates (29 preterm and 21 full-term infants). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to genotype MBL2 gene exon 1 (rs1800450) and (rs1800451) SNPs. Enzyme-linked immunosorbent assay (ELISA) was used to measure MBL serum concentrations. Results The polymorphic genotypes BB and AC at codons 54 and 57, respectively, showed higher frequencies than the wild-type genotype (AA) (14.1% versus 12.9% and 28.1% versus 19.4% respectively) in both groups, and this difference was greater in the septic group than in the non-septic group; however, the differences did not reach statistical significance. The B and C allele frequencies were also higher in the septic group than in the non-septic group, but the differences did not reach statistical significance ( p = 0.282 and 0.394, respectively). The serum levels of MBL were significantly lower in the septic group than in the non-septic group ( p = 0.028). Conclusion This study found no association between MBL levels or MBL2 exon 1 genotypes or alleles and neonatal sepsis risk. Further studies with larger sample sizes are needed to determine the role of the MBL2 gene as a risk factor and early predictor of neonatal sepsis.

Mannose-binding lectin genotypes and outcome in end-stage renal disease: a prospective cohort study.

Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft. A total of 98 patients with ESRD accepted for living-donor renal transplantation or on the waiting list for transplantation were included and prospectively followed for an average of 9 years (range 7.5-9.9). Medical records were evaluated regarding transplantation status, diabetes mellitus, vascular parameters and infections for all the patients. Cox regression models and logistic regression analysis were used for statistical analyses. The cohort was divided into two groups according to the MBL2 genotype (normal A/A versus variant A/O or O/O). We found no evidence for an association between the MBL2 genotype and all-cause mortality, cardiovascular events or bacterial infections (pneumonia, urinary tract infection, fistula infection or other infections). In this cohort, the MBL2 genotype did not seem to be associated with any long-term clinical effects in ESRD patients on dialysis or with a functioning graft.

Autosomal dominant mannose-binding lectin deficiency is associated with worse neurodevelopmental outcomes after cardiac surgery in infants

ObjectivesThe MBL2 gene is the major genetic determinant of mannose-binding lectin (MBL)—an acute phase reactant. Low MBL levels have been associated with adverse outcomes in preterm infants. The MBL2Gly54Asp missense variant causes autosomal dominant MBL deficiency. We tested the hypothesis that MBL2Gly54Asp is associated with worse neurodevelopmental outcomes after cardiac surgery in neonates. MethodsThis is an analysis of a previously described cohort of patients with nonsyndromic congenital heart disease who underwent cardiac surgery with cardiopulmonary bypass before age 6 months (n = 295). Four-year neurodevelopment was assessed in 3 domains: Full-Scale Intellectual Quotient, the Visual Motor Integration development test, and the Child Behavior Checklist to assess behavior problems. The Child Behavior Checklist measured total behavior problems, pervasive developmental problems, and internalizing/externalizing problems. A multivariable linear regression model, adjusting for confounders, was fit. ResultsMBL2Gly54Asp was associated with a significantly increased covariate-adjusted pervasive developmental problem score (β = 3.98; P = .0025). Sensitivity analyses of the interaction between age at first surgery and MBL genotype suggested effect modification for the patients with MBL2Gly54Asp (Pinteraction = .039), with the poorest neurodevelopment outcomes occurring in children who had surgery earlier in life. ConclusionsWe report the novel finding that carriers of MBL2Gly54Asp causing autosomal dominant MBL deficiency have increased childhood pervasive developmental problems after cardiac surgery, independent of other covariates. Sensitivity analyses suggest that this effect may be larger in children who underwent surgery at earlier ages. These data support the role of nonsyndromic genetic variation in determining postsurgical neurodevelopment-related outcomes in children with congenital heart disease.

Mannose-Binding Lectin (MBL) gene polymorphisms in susceptibility to pulmonary tuberculosis among the Lur population of Lorestan Province of Iran

ObjectiveTuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL polymorphisms and TB has been studied in various populations, the results are controversial. The aim of this study was to investigate mannose-binding lectin (MBL) gene polymorphisms with susceptibility to pulmonary tuberculosis (PTB) in a Lur population of Iran. MethodsIn this case-control study, four functional MBL gene polymorphisms (HL, XY, PQ and AB) were genotyped by using PCR Single Strand Conformation Polymorphism (SSCP) technique in a Lur population living in Lorestan Province, consisting of 100 patients with pulmonary tuberculosis (PTB) age and sex matched 100 healthy controls (HCs). Association analyses were performed with the SPSS 21 statistical software. ResultsWe found that MBL (HH) genotype polymorphism significantly was associated with increased susceptibility to TB (35% in patients vs. 22% in controls, P=0.0417, OR=1.909, %95 CI=1.020–3.573). Additionally, H allele showed a significant association with increased risk of TB (56.5% in patients vs. 46% in controls, P=0.0357, OR=1.525, %95 CI=1.028–2.262). Also, the distribution of L allele in patients was significantly lower frequency in TB patients compared to controls (43.5% vs. 54%, P=0.0357, OR=0.656, %95 CI=0.442–0.973). However, the allelic and genotypic frequencies of AB, XY and PQ polymorphisms were not significantly different between the patients and the controls. We couldn't detect any significant differences between haplotypes among TB patients and healthy controls. ConclusionsOur findings demonstrated that HH genotype and H allele may increase the susceptibility to pulmonary TB in the Lur population of Iran, although L allele may decrease the susceptibility to pulmonary TB in this population. We suggest that it is necessary to further more studies with larger sample size and other ethnic population.

High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele

BackgroundIn-stent restenosis occurs in 10–30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation.MethodsIn a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression.ResultsAverage follow-up time was 1.0 (+ − 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ − 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis.ConclusionsMBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism.

Mannose-binding lectin in chronic hepatitis C in children

Objective. To investigate effect of mannose-binding lectin (MBL) genetic polymorphisms and phenotype in chronic hepatitis C and its impact on response to antiviral therapy in children. Methods. Fifty four children with chronic hepatitis C, aged 2.5–18 years were enrolled. Forty-five children were treated with interferon-α (IFN-α) alone (n = 2) or IFN-α and ribavirin (n = 43). Twenty-one children who responded to antiviral therapy were defined as sustained responders to therapy (IFN-SR). Before therapy, MBL genotypes and serum MBL levels (by ELISA) were determined. MBL genotype distribution and levels were correlated to disease characteristics and response to therapy. Results. Children with chronic hepatitis C who did not respond to antiviral therapy (IFN-NR) presented more frequently MBL2 polymorphisms, although this did not reach significance (p = 0.08). MBL levels were significantly lower in children classified as IFN-NR when compared to children defined as IFN-SR (1.623 ng/ml vs. 3.699 ng/ml), (p = 0.04). Serum activity levels of ALT and AST were higher in children with A/O MBL genotype when compared to group with A/A genotype (p < 0.05). Conclusions. Our findings suggest negative effect of MBL deficiency (defined by genotype and phenotype) on progression of chronic hepatitis C in children and response to antiviral therapy.

Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis.

BackgroundMannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB).MethodA total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions.ResultsBoth genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P < 0.05, OR 1.393, 1.302 and 1.426 respectively). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was 0.897 (95% CI: 0.282, 1.513) and 1.142 (95% CI: 0.755, 1.530) respectively (P < 0.05).ConclusionPolymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with the susceptibility of TB, and there were gene-gene interactions among them.

Mannose binding lectin (MBL) 2 gene polymorphism & its association with clinical manifestations in systemic lupus erythematosus (SLE) patients from western India.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies. Mannose binding lectin (MBL) is an important element of the innate defense system. t0 he present study was undertaken to determine whether variant alleles in MBL2 gene were associated with disease severity in SLE patients. The MBL alleles [-550, -221, +4, Codon 52, Codon 54 and Codon 57] were studied by PCR- RFLP (restriction fragment length polymorphism) method in 100 SLE patients fulfilling ACR (American College of Rheumatology) criteria along with 100 healthy controls. SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) score. Homozygosity for MBL variant allele (O/O) was observed in 24 per cent of the SLE patients compared to 16 per cent of the normal controls, while no difference was found for heterozygosity (A/O) (37 vs 35%). A significant difference was reported in incidence of double heterozygosity for mutant allele B and D (B/D) among SLE patients as against control group ( p = 0.015). MBL genotypes did not show any association with renal involvement. In this study from western India, MBL gene polymorphism showed an influence as a possible risk factor for susceptibility to SLE, but had no direct effect on disease characteristics. Further studies need to be done on a larger number of SLE patients in different regions of the country.

Extreme high prevalence of a defective mannose-binding lectin (MBL2) genotype in native South American West Andean populations.

Mannose-binding lectin (MBL) is one of the five recognition molecules in the lectin complement pathway. Common variant alleles in the promoter and structural regions of the human MBL gene (MBL2) influence the stability and serum concentration of the protein. Epidemiological studies have shown that MBL2 variant alleles are associated with susceptibility to and the course of different types of infectious and inflammatory conditions. However, it has been suggested that these alleles are maintained in different populations due to selected advantages for carriers. We investigated the MBL2 allelic variation in indigenous individuals from 12 different West Central South America localities spanning from the desert coast, high altitude Andean plates and the Amazon tropical forest within the territories of Peru (n = 249) (Departments of Loreto, Ucayali, Lambayeque, Junin, Ayacucho, Huancayo and Puno), and Ecuador (n = 182) (Region of Esmeraldas and Santo Domingo de los Colorados). The distribution of MBL2 genotypes among the populations showed that the defective variant LYPB haplotype was very common. It showed the highest frequencies in Puno (Taquile (0.80), Amantani (0.80) and Anapia (0.58) islander communities of the Lake Titicaca), but lower frequencies of 0.22 in Junin (Central Andean highland) and Ucayali (Central Amazonian forest), as well as 0.27 and 0.24 in the Congoma and Cayapa/Chachis populations in the Amazonian forest in Ecuador were also observed. Our results suggest that the high prevalence of the MBL2 LYPB variant causing low levels of functional MBL in serum may mainly reflect a random distribution due to a population bottleneck in the founder populations.

Impact of passive smoking, cooking with solid fuel exposure, and MBL/MASP-2 gene polymorphism upon susceptibility to tuberculosis

To explore the impact of passive smoking, cooking with solid fuel, mannose-binding lectin (MBL) gene, MBL-associated serine proteases 2 (MASP-2) gene, and gene-environment interactions on the susceptibility to tuberculosis (TB) in non-smokers. A total of 205 TB patients and 216 healthy controls were recruited to participate in this case-control study. PCR with sequence-specific primers (PCR-SSP) technology was leveraged to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and information on exposures of participants were collected. Unconditioned logistic regression analysis was conducted to identify associations between the various factors and TB, and marginal structural linear odds models were used to estimate the interactions. Passive smoking and cooking with solid fuel were associated with the risk of TB, with odds ratios (OR) of 1.58 and 2.93, respectively (p<0.05). Genotype CG at rs7096206 of MBL genes (OR 2.02) and genotype TC at rs6695096 of MASP-2 genes (OR 1.67) were more prevalent in the TB patients than in healthy controls (p<0.05). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and passive smoking or cooking with solid fuel exposure was 1.86 (95% confidence interval (CI) 0.59-3.16) and 2.66 (95% CI 1.85-3.47), respectively. The RERI between rs6695096 of MASP-2 genes and cooking with solid fuel exposure was 3.70 (95% CI 2.63-4.78), which was also a positive interaction. However, the RERI between rs6695096 of MASP-2 genes and passive smoking was not statistically significant. Passive smoking, cooking with solid fuel, and polymorphisms of MBL (rs7096206) and MASP-2 (rs6695096) genes were associated with susceptibility to TB in non-smokers, and there were gene-environment interactions among them. Further studies are needed to explore details of the mechanisms of association.