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Association of mannose binding lectin with chronic obstructive pulmonary disease susceptibility and its clinical
Aarti Sharma1, Shreya Singh Kashyap1, Nirmal Chand Kajal2
1Department of Human Genetics, Guru Nanak Dev University, Amritsar, Pb, 143005, India.
Background:
The physiological interactions of MBL suggest its contribution towards the pathogenesis of COPD.
Objective:
The present case-control study was undertaken to elucidate the role of MBL with COPD risk and clinical outcomes in north Indian cohort.
Methods:
Patients were enrolled as per GOLD criteria. MBL2 variants were selected based on the literature and their putative functional significance. Genotyping of six single nucleotide polymorphisms of MBL2 comprising of two coding (rs1800450, rs1800451) and four non-coding variants (rs11003125, rs7096206, rs11003123 and rs7095891) was done by using PCR-RFLP and ARMS-PCR. Serum MBL levels were analysed by sandwich ELISA.
Results:
Overall findings of the molecular genetic analysis of MBL2 indicated significant difference in frequency of three of the six studied variants, between patients and controls or among different disease severity stages. Heterozygous genotype of rs7095891 showed significant protective association towards severity of disease. Linkage disequilibrium (LD) analysis indicated a strong LD between rs1800450 and rs7095891 while intermediate LD was observed for rs11003123/rs11003125 and rs7096206/rs11003125. Haplotype analysis revealed 17.14-fold risk of developing exacerbations conferred by GGGTGG haplotype. Significantly low serum MBL levels observed in COPD patients as compared to controls. Significant difference in MBL deficiency levels were also observed for homozygous wild and variant genotypes of rs11003125 and rs7096206 respectively, as well as for all genotypes of rs11003123 than respective controls.
Conclusion:
The present study reinforces the role played by MBL in the susceptibility, protection and clinical outcomes of COPD. Therefore, including the reported associations at diagnostic, prognostic and therapeutic interventions may prove helpful.
Insights
This study found that Mannose-binding lectin (MBL) gene variants and serum levels are linked to Chronic Obstructive Pulmonary Disease (COPD) risk and severity. MBL plays a role in COPD susceptibility, protection, and outcomes.
Area of Science:
- Immunogenetics
- Pulmonology
- Genetic Epidemiology
Background:
- Physiological interactions of Mannose-binding lectin (MBL) suggest its involvement in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis.
- Understanding MBL's role is crucial for COPD management.
Purpose of the Study:
- To investigate the association between MBL gene variants and serum MBL levels with COPD risk and clinical outcomes in a North Indian population.
- To elucidate the genetic and molecular basis of MBL's contribution to COPD.
Main Methods:
- Case-control study design enrolling patients based on GOLD criteria.
- Genotyping of six MBL2 single nucleotide polymorphisms (SNPs) using PCR-RFLP and ARMS-PCR.
- Quantification of serum MBL levels via sandwich ELISA and analysis of linkage disequilibrium and haplotype frequencies.
Main Results:
- Significant differences in the frequencies of three MBL2 variants between COPD patients and controls, or across disease severity stages.
- A protective association of the heterozygous genotype rs7095891 with disease severity and a 17.14-fold increased risk of exacerbations with the GGGTGG haplotype.
- Significantly lower serum MBL levels in COPD patients compared to controls, with MBL deficiency linked to specific MBL2 genotypes.
Conclusions:
- The study confirms MBL's significant role in COPD susceptibility, protection, and clinical outcomes.
- Findings support the potential utility of MBL in diagnostic, prognostic, and therapeutic strategies for COPD.
- Genetic variations in MBL2 influence COPD risk and severity, highlighting its importance in respiratory health.
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