Department of Human Genetics, Guru Nanak Dev University, Amritsar, Pb, 143005, India.
Department of Pulmonary Medicine, Government Medical College, Amritsar, Pb, 143001, India.
Mol Biol Rep. 2023 Oct;50(10):8145-8161. doi: 10.1007/s11033-023-08617-9. Epub 2023 Aug 9.
The physiological interactions of MBL suggest its contribution towards the pathogenesis of COPD.
The present case-control study was undertaken to elucidate the role of MBL with COPD risk and clinical outcomes in north Indian cohort.
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.
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.
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.
MBL 的生理相互作用表明其对 COPD 发病机制的贡献。
本病例对照研究旨在阐明 MBL 在北印度队列中 COPD 风险和临床结局中的作用。
根据 GOLD 标准招募患者。根据文献和推测的功能意义选择 MBL2 变体。使用 PCR-RFLP 和 ARMS-PCR 对 MBL2 的六个单核苷酸多态性（包括两个编码（rs1800450、rs1800451）和四个非编码变体（rs11003125、rs7096206、rs11003123 和 rs7095891）进行基因分型。通过夹心 ELISA 分析血清 MBL 水平。
MBL2 分子遗传分析的总体结果表明，在患者和对照组或不同疾病严重程度阶段之间，六个研究变体中的三个变体的频率存在显著差异。rs7095891 的杂合基因型对疾病严重程度表现出显著的保护作用。连锁不平衡（LD）分析表明，rs1800450 和 rs7095891 之间存在强 LD，而 rs11003123/rs11003125 和 rs7096206/rs11003125 之间存在中等 LD。单体型分析显示 GGGTGG 单体型使发生恶化的风险增加了 17.14 倍。与对照组相比，COPD 患者的血清 MBL 水平明显降低。rs11003125 和 rs7096206 的纯合野生和变体基因型以及所有 rs11003123 基因型与相应对照相比，MBL 缺乏水平也存在显著差异。
本研究进一步证实了 MBL 在 COPD 的易感性、保护和临床结局中的作用。因此，包括在诊断、预后和治疗干预中报告的关联可能会有所帮助。
