Genetic susceptibility to COPD: Systematic review, bibliometric analysis and meta-analysis of SERPINA1, HHIP, IREB2,
Sanjukta Dasgupta1, Subhangi Duttagupta2, Pranay Patra3
1Centre for Multidisciplinary Research and Innovations, Brainware University, 398 Ramkrishnapur Road, Barasat, Kolkata, West Bengal, 700125, India; Department of Biotechnology, Brainware University, 398 Ramkrishnapur Road, Barasat, Kolkata, West Bengal, 700125, India.
Background:
Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder influenced by environmental exposures and genetic susceptibility. Despite numerous studies, the effects of key susceptibility genes remain inconsistent across populations, and their overall clinical relevance is unclear.
Methods:
Following PRISMA guidelines and registered in PROSPERO (ID: CRD420251077565), we conducted a systematic review and meta-analysis of studies published between 2010 and 2025. Eighteen unique studies were included, ranging from small cohorts (n = 36) to large biobank analyses (∼4.5 million participants), collectively evaluating five candidate genes: SERPINA1, HHIP, IREB2, SFTPD, and FAM13A. Pooled hazard ratios (HRs) were calculated, with subgroup analyses by ethnicity and variant-level differences. Associations with spirometric parameters (FEV1, FEV1/FVC) were examined to assess clinical relevance.
Results:
SERPINA1 demonstrated the strongest significant with COPD (HR = 2.47). A significant association was also observed for SFTPD, although based on fewer studies. Subgroup analysis by ethnicity/geographical region revealed the highest pooled risk in East Asians (HR = 2.18), significant associations in Europeans (HR = 1.46) and Americans (HR = 1.47), and a weaker or potentially protective effect in Oceania (HR = 0.67). SERPINA1 risk correlated with lung function decline (FEV1: r = -0.64; FEV1/FVC: r = -0.71), highlighting translational relevance.
Conclusions:
SERPINA1 emerges as the most clinically relevant genetic determinant of COPD, linking susceptibility to measurable spirometric impairment, with effects varying by ethnicity. These findings emphasize the need for genetic screening integrated with lung function assessment and ethnicity-specific risk stratification to advance precision management of COPD.
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