Department Of Human Genetics And Molecular Medicine

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Author: search.filters.author.Senapati, SabyasachiSubject: search.filters.subject.COPD

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    Serum homocysteine could be used as a predictive marker for chronic obstructive pulmonary disease: A meta-analysis
    (Frontiers Media S.A., 2019) Chaudhary, D; Sharma, N; Senapati, Sabyasachi
    Background: Serum homocysteine (Hcy) level is inversely related with concentration of folic acid, which is an essential micronutrient for metabolism and energy homeostasis. Serum concentrations of Hcy have been reported to have strong correlation with smoking, which is a major risk factor for pathogenesis of chronic obstructive pulmonary disease (COPD) irrespective of ethnicity and gender. Therefore, we performed a systematic review based meta-analysis to evaluate the overall contribution of Hcy in COPD. Method: Published literature on association of serum Hcy with COPD were obtained through conventional web search and eligible literature were selected based on stringent inclusion/exclusion criteria. Continuous variable data was presented as mean and standard deviation. The variable data was analyzed using RevMan 5 statistical tool to meta-analyze mean differences (MD) with 95 % CI for case-control studies. Result: Four case-control studies met the inclusion criteria for this study. A total of 145 COPD subjects and 107 healthy controls were analyzed. Elevated serum homocysteine concentration was found to induce risk for COPD (MD = 3.05). Conclusion: Molecular role of Hcy in COPD pathogenesis or prognosis is not clear but existing literature suggests that smoking disturbs folic acid metabolism and promotes Hcy accumulation. This study suggested the contribution of Hcy in COPD pathogenesis. However, large scale prospective cohort study and replication studies with more power are warranted to confirm the results. © 2019 Chaudhary, Sharma and Senapati.
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    Systematic review and meta-analysis confirms significant contribution of surfactant protein D in chronic obstructive pulmonary disease
    (Frontiers Media S.A., 2019) Nandy, D; Sharma, N; Senapati, Sabyasachi
    Background: Surfactant protein D (SFTPD) is a lung specific protein which performs several key regulatory processes to maintain overall lung function. Several infectious and immune mediated diseases have been shown to be associated with SFTPD. Recent findings have suggested the serum concentration of SFTPD can be used as a diagnostic or prognostic marker for chronic obstructive pulmonary disease (COPD) and acute exacerbation COPD (AECOPD). But these findings lack replication studies from different ethnic populations and meta-analysis, to establish SFTPD as reliable diagnostic or prognostic biomarker for COPD and associated conditions. Methods: We performed systematic literature search based on stringent inclusion and exclusion criteria to identify eligible studies to perform a meta-analysis. Our objective was to assess the predictability of serum SFTPD concentration and SFTPD allelic conformation at rs721917 (C > T) with COPD and AECOPD outcome. These variables were compared between COPD and healthy controls, where mean difference (MD), and odds ratio (OR) were calculated to predict the overall effect size. Review manager (RevMan-v5.3) software was used to analyse the data. Results: A total of eight published reports were included in this study. Comparative serum SFTPD concentration data were extracted from six studies and three studies were evaluated for assessment of genetic marker from SFTPD. Our study identified strong association of elevated serum SFTPD with COPD and AECOPD. Significant association of risk was also observed for "T" allele or "TT" genotype of rs721917 from SFTPD with COPD and AECOPD. Conclusion: Serum concentration and alleleic conformation of SFTPD has a significantly high predictive value for COPD and AECOPD. Thus, these can be tested further and could be applied as a predictive or prognostic marker. © 2019 Frontiers Media S.A. All Rights Reserved.
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    Systematic review and meta-analysis to establish the association of common genetic variations in Vitamin D binding protein with chronic obstructive pulmonary disease
    (Frontiers Media S.A., 2019) Khanna, R; Nandy, D; Senapati, Sabyasachi
    Background: Vitamin-D binding protein (DBP) also known as GC protein, is a major determinant for vitamin- D metabolism and transport. GC1F, GC1S, and GC2 are the three allelic variants (denoted as rs4588 and rs7041) of GC, and known to be associated with chronic obstructive pulmonary disease (COPD). However, contradictory reports and population specific risk attributed by these alleles warranted detailed genetic epidemiology study to establish the association between GC variants and COPD. In this study we performed a meta-analysis and investigated the genetic architecture of GC locus to establish the association and uncover the plausible reason for allelic heterogeneity. Methods: Published cross-sectional case control studies were screened and meta-analysis was performed between GC variants and COPD outcome. RevMan-v5.3 software was used to perform random and/or fixed models to calculate pooled odds ratio (Meta-OR). Linkage disequilibrium (LD) and haplotypes at GC locus were evaluated using 1000 Genomes genotype data. In silico functional implications of rs4588 and rs7041 was tested using publicly available tools. Results: GC1F allele and GC1F/1F genotype were found to confer COPD risk in overall meta-analysis. GC1S/1S was found to confer risk only among Europeans. In silico investigation of rs4588 and rs7041 identified strong eQTL effects and potential role in regulation of GC expression. Large differences in allele frequencies, linkage disequilibrium (LD) and haplotypes were identified at GC locus across different populations (Japanese, African, Europeans, and Indians), which may explain the variable association of different GC alleles in different populations. Conclusion: GC1F and GC1F/1F impose significant genetic risk for COPD, among Asians. Considerable differences in allele frequencies and LD structure in GC locus may impose population specific risk. Copyright © 2019 Khanna, Nandy and Senapati. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.