Novel Polymorphism In A Promoter Of MBL2 Gene Result In Lower MBL Expression In Chronic Infection Caused By HCV

The Pathogen Recognition Receptors (PRRs) is an active protein in the immune system. The PRRs that secreted in the liver and we addressed were L-ficolin, MBL and H-ficolin. Previous studies revealed that both MBL and L-ficolin were hampered the HCV entry and infectivity. However, H-ficolin impact still needs to be addressed more so as determining their role during HCV infection. For these purposes, we aimed to determine the effect of different level in the serum of these proteins on the HCV infection and treatment outcome. Initially, we selected (25) HCV positive patients and (25) HCV negative control patients from the Trent Cohort and Regional Haemophiliac Study and to present the differences in serum concentrations of MBL, H- and L-ficolin. The level of these proteins was measured by ELISA method and compared with each other based on the detected SNPs by PCR and sequencing methods in the responsible genes. Our results showed that the polymorphism at position -221 in the MBL2 promoter significantly reduce the level of MBL protein more than the SNP at position -551. Interestingly, a new deletion of six nucleotides [AGGAAG] detected in the promoter at position -319 to -324 that succeeded by four other mutations at position -328, -336, -349 and -427 in most of the analyzed sequences. The 6bp deletion was statistically decreasing the concentration of MBL below 1µg.mL-1, precisely among non-responder patients. In conclusion, the existence of the new deletion in the promoter region of MBL2 gene and the additional newly detected polymorphisms, reduce the level of MBL protein and as a result impacts on the response to treatment among HCV-infected patients.

Genetic risk factors for hepatitis B

В работе в качестве материала для исследования были использованы образцы ДНК, выделенные из крови 99 людей в возрасте от 20 до 80 лет, из них 47 человек инфицированы вирусом гепатита В и 52 человека без вирусной нагрузки. По результатам исследования установлено, что аллель А полиморфизма rs1800450 гена MBL2 ассоциирован с высоким риском развития гепатита В, а наличие генотипа GG снижает такой риск; взаимодействие полиморфных вариантов гена STAT3 с генотипом GG гена MBL2 снижает риск развития гепатита В. DNA samples extracted from the blood of 99 people aged 20 to 80 years were used as the material for our research. Among these people 47 were infected with HBV and 52 were not. The reseach found that the allele A of the rs1800450 polymorphism of the MBL2 gene is associated with a high risk of hepatitis B, and the presence of the GG genotype reduces this risk; interaction of polymorphic variants of the STAT3 gene with a GG genotype of the MBL2 gene reduces the risk of hepatitis B.

Lack of associations between lactoferrin (LTF) and mannose-binding lectin 2 (MBL2) gene polymorphism and dental caries susceptibility

Objective With the development of human genomics, the genetic factors associated with dental caries have receiving increasing attention. This study was performed to evaluate the relationship between lactoferrin ( LTF) and mannose-binding lectin 2 ( MBL2) gene single nucleotide polymorphisms (SNPs) and dental caries susceptibility in Chinese children. Methods This prospective case–control study included 360 unrelated children (aged 12–15 years) who received oral health examinations and questionnaire surveys. The children were divided into two groups by counting the numbers of decayed, missing, and filled teeth (DMFT/dmft): case group (n = 162, DMFT/dmft ≥ 1) and control group (n = 198, DMFT/dmft = 0); non-invasive saliva samples were collected to extract genomic DNA. Six SNPs ( rs2073495C/G, rs1042073C/T, rs10865941C/T, and rs1126477A/G in LTF; rs7096206C/G and rs7095891G/A in MBL2) were tested by mass spectrometry. Results The study included 360 individuals with (85 boys and 77 girls) and without a history of caries (96 boys and 102 girls). There were no statistically significant differences in alleles and genotypes among the six SNPs between the two groups. Conclusion There is no evidence that polymorphisms of LTF and MBL2 genes are associated with dental caries susceptibility in populations from northwest China; further confirmation is needed with larger sample sizes.

MBL2 gene polymorphisms are not related to the occurrence of cerebrovascular disease in sickle cell anemia

Objective: This study has as objective to verify whether MBL2 gene polymorphisms are related to the occurrence of cerebrovascular disease (CD) in sickle cell anemia (SCA) patients. Methods: Overall, 259 unrelated SCA patients were enrolled. The patients were divided into three groups: control group, stroke group ad range of risk group. Peripheral blood samples were collected and DNA extraction was performed. All patients were genotyped for exon 1, promoter region -221 and promoter region -550 of MBL2 gene, along with β-globin gene haplotypes. Results: Concerning the genotyping of the MBL2, there was no difference in the frequency of allelic and genotypic variants of the exon 1 and the promoter regions -221 and -550 of the MBL2 gene among the studied groups. Conclusion: Despite the small number of patients, and the lack of association between MBL2 polymorphisms and CD, our study represents an effort to understand the impact of MBL2 polymorphisms in the clinical outcome of patients with SCA.

Association Study of MBL2 Gene Polymorphisms and Risk of Tuberculosis in Southeast of Iran

Mannose-binding lectin (MBL) is an acute phase protein which recognizes the pathogens through its carbohydrate recognition domain. It is an important part of human innate immunity. The aim of the current study was to evaluate the impact of MBL2 polymorphism on pulmonary tuberculosis in a number of patients from the southeast of Iran. In this case-control study, 2 MBL gene polymorphisms (rs1800450, rs7095891) were genotyped using PCR-RFLP method and polymerase chain reaction for detection of 34bp ins/del of MBL2 gene (rs777980157) polymorphism. The study included 170 patients with PTB (pulmonary tuberculosis) and 175 control subjects. The findings indicated that the GA (GA vs. GG: OR=0.172, 95% CI=0.107–0.275, P<0.001) (OR – odds ratio; CI – confidence interval) genotype as well as GA+AA (GA+AA vs. GG: OR=0.191, 95% CI=0.120–0.302, P<0.001) genotype of rs1800450 reduced the risk of PTB compared to GG genotype. The rs7095891 variant significantly decreased the risk of PTB in codominant (GA vs. GG: OR=0.118, 95% CI=0.054–0.258, P<0.001; and AA vs. GG: OR=0.029, 95% CI=0.01–0.082, P<0.001), dominant (GA+AA vs. GG: OR=0.095, 95% CI=0.044–0.207, P<0.001) and recessive (AA vs. GA+GG: OR=0.172, CI=0.081–0.365, P<0.001) inheritance models. No significant relationship was identified between the rs777980157 variant and PTB risk/protection. In conclusion, we found that the MBL2 rs1800450 and rs7095891 polymorphisms provide relative protection against PTB. Additional studies on larger populations with different ethnicities are required to verify our findings.