BPIFB4 rs4339026 A > G polymorphism impacts COPD susceptibility in the Kashi population, China.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40280985", "kind": "science-record", "revision": 3, "content_hash": "sha256:92d87b482f1bbf0a82c3226242bcada16f74770ce26f1b796e4cc33028d31cbb", "created_at": "2026-11-01T20:30:26Z", "updated_at": "2026-11-01T22:13:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "BPIFB4 rs4339026 A > G polymorphism impacts COPD susceptibility in the Kashi population, China.", "doi": "10.1038/s41598-025-98599-4", "pmid": "40280985", "authors": ["Jingran Xu", "Li Tao", "Yanyan Shi", "Hui Gong", "Zulipikaer Abudureheman", "Aifang Zheng", "Xuemei Zhong", "Lexin Xue", "Xiaoguang Zou", "Li Li"], "journal": "Scientific reports", "year": 2025, "abstract": "The etiology of chronic obstructive pulmonary disease (COPD) is multifaceted. This study aims to explore the association between the bactericidal/permeability-increasing bold-containing family B member 4 (BPIFB4) rs4339026 A > G (NC_000,020.11: g.33083793 A > G) polymorphism and COPD susceptibility in Kashi population, and investigate the potential role of BPIFB4 in COPD. A total of 541 unrelated COPD patients and 534 healthy controls were enrolled from the First People's Hospital and Kashi village. The association between rs4339026 A > G polymorphism and COPD risk were assessed by multivariable logistic regression. BPIFB4 expression and associated pathways were analyzed through bioinformatics approaches using human peripheral blood and bronchoalveolar lavage fluid (BALF) datasets from the GEO database (GSE13896 and GSE42057). Experimental validation was performed in a cigarette smoke (CS)-induced COPD mouse model. BPIFB4 rs4339026 G/G genotype was associated with significantly increased COPD risk across all genetic models: genotype model [adjusted odds ratios (aOR) = 2.52, corresponding 95% confidence interval (95% CI): 1.34-4.71], recessive model (aOR = 2.32, 95% CI: 1.25-4.31), dominant model (aOR = 1.39, 95% CI: 1.07-1.81), allele model (aOR = 1.42, 95% CI: 1.13-1.77), and additive model (aOR = 1.40, 95% CI: 1.12-1.75). Stratified analysis based on smoking status revealed that BPIFB4 rs4339026 G/G genotype was also associated with an increased risk of COPD, regardless of smoking status. However, the risk was more pronounced in smokers compared to non-smokers, as evidenced by the dominant model (aOR = 2.52, 95% CI: 1.23-5.15), additive model (aOR = 2.61, 95% CI: 1.37-4.97), and allele model (aOR = 2.68, 95% CI: 1.41-5.08). In non-smokers, the association remained significant, with the genotype model (aOR = 1.99, 95% CI: 1.03-3.85), additive model (aOR = 1.28, 95% CI: 1.01-1.62), and allele model (aOR = 1.29, 95% CI: 1.01-1.64). The bioinformatics analysis demonstrated a decrease in BPIFB4 expression in peripheral blood and BALF of COPD patients, with pathway enrichment analysis implicating PI3K/AKT signaling. Consistently, COPD mice exhibited significant BPIFB4 downregulation (P < 0.0001), accompanied by upregulation of PI3K, p-PI3K, and p-AKT was upregulated (P < 0.001 vs. controls). We confirmed that BPIFB4 rs4339026 A > G increased the risk of COPD. BPIFB4 might contribute to COPD pathogenesis through the PI3K/AKT pathway.", "claims": [{"id": "claim-method", "statement": "Multivariable logistic regression analysis was performed to calculate aORs with 95%CIs, adjusting for sex, age, BMI, smoking status, FEV1%, and FEV1/FVC, to examine the association between rs4339026 A > G and COPD risk.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40280985", "locator": "sections[21] \"Statistical analysis\" paragraph 3", "quote": "Multivariable logistic regression analysis was performed to calculate aORs with 95%CIs, adjusting for sex, age, BMI, smoking status, FEV1%, and FEV1/FVC, to examine the association between rs4339026 A > G and COPD risk."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the NCBI Sequence Read Archive (SRA) repository under accession number PRJNA785331.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40280985", "locator": "sections[27] \"notes\" paragraph 1", "quote": "The datasets generated and/or analyzed during the current study are available in the NCBI Sequence Read Archive (SRA) repository under accession number PRJNA785331."}], "state": "complete"}, {"id": "claim-target-result", "statement": "After correcting for sex, age, BMI, smoking status, FEV1% and FEV1/FVC, the G/G genotype of BPIFB4 rs4339026 A > G was significantly elevated the risk of COPD under multiple genetic models: genotype model [adjusted odds ratio (aOR) = 2.52, corresponding 95% confidence interval (95% CI): 1.34–4.71], recessive model (aOR = 2.32, 95% CI: 1.25–4.31), and dominant model (aOR = 1.39, 95% CI: 1.07–1.81).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40280985", "locator": "sections[5] \"Genotypic analysis of BPIFB4 rs4339026 A > G in the case-control study\" paragraph 2", "quote": "After correcting for sex, age, BMI, smoking status, FEV1% and FEV1/FVC, the G/G genotype of BPIFB4 rs4339026 A > G was significantly elevated the risk of COPD under multiple genetic models: genotype model [adjusted odds ratio (aOR) = 2.52, corresponding 95% confidence interval (95% CI): 1.34–4.71], recessive model (aOR = 2.32, 95% CI: 1.25–4.31), and dominant model (aOR = 1.39, 95% CI: 1.07–1.81)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "After correcting for sex, age, BMI, smoking status, FEV1% and FEV1/FVC, the G/G genotype of BPIFB4 rs4339026 A > G was significantly elevated the risk of COPD under multiple genetic models: genotype model [adjusted odds ratio (aOR) = 2.52, corresponding 95% confidence interval (95% CI): 1.34–4.71], recessive model (aOR = 2.32, 95% CI: 1.25–4.31), and dominant model (aOR = 1.39, 95% CI: 1.07–1.81).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40280985"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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