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SNP and Haplotype Interaction Models Reveal Association of Surfactant Protein Gene Polymorphisms With Hypersensitivity Pneumonitis of Mexican Population.

ABSTRACT: Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of common environmental organic particles. Surfactant proteins (SPs) play a role in innate immunity and surfactant function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes of the SP genes associate with HP. Methods: Seventy-five HP patients caused by avian antigen and 258 controls, asymptomatic antigen exposed and non-exposed were enrolled. SNP association was performed using logistic regression analysis and SNP-SNP interaction models. Results: Based on odds ratio, regression analyses showed association of (a) rs7316_G, 1A³ (protective) compared to antigen exposed; (b) male sex, smoking, rs721917_T and rs1130866_T (protective) compared to non-exposed controls with HP; (c) compared to antigen exposed, 25 interactions associated with HP in a three-SNP model; (d) compared to non-exposed, (i) rs1136451 associated with increased, whereas rs1136450 and rs1130866 associated with lower HP risk, (ii) 97 interactions associated with HP in a three-SNP model. The majority of SNP-SNP interactions associated with increased HP risk involved SNPs of the hydrophilic SPs, whereas, the majority of interactions associated with lower HP risk involved SNPs of both hydrophilic and hydrophobic SPs; (e) haplotypes of SP genes associated with HP risk. Conclusions: The complexity of SNPs interactions of the SFTP genes observed indicate that the lung inflammatory response to avian antigens is modulated by a complex gene interplay rather than by single SNPs.

SUBMITTER: Gandhi CK

PROVIDER: S-EPMC7813780 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SNP and Haplotype Interaction Models Reveal Association of Surfactant Protein Gene Polymorphisms With Hypersensitivity Pneumonitis of Mexican Population.

Gandhi Chintan K CK Chen Chixiang C Amatya Shaili S Yang Lili L Fu Chenqi C Zhou Shouhao S Wu Rongling R Buendía-Roldan Ivette I Selman Moisés M Pardo Annie A Floros Joanna J

Frontiers in medicine 20210105

<b>Background:</b> Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of common environmental organic particles. Surfactant proteins (SPs) play a role in innate immunity and surfactant function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes of the SP genes associate with HP. <b>Methods:</b> Seventy-five HP patients caused by avian antigen and 258 controls, asymptomatic antigen exposed and non-exposed were enrolled. SNP association w ...[more]

PMID: 33469544

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Project description:Surfactant proteins (SPs) are important for normal lung function and innate immunity of the lungs and their genes have been identified with significant genetic variability. Changes in quantity or quality of SPs due to genetic mutations or natural genetic variability may alter their functions and contribute to the host susceptibility for particular diseases. Alternatively, SP single nucleotide polymorphisms (SNPs) can serve as markers to identify disease risk or response to therapies, as shown for other genes in a number of other studies. In the current study, we evaluated associations of SFTP SNPs with idiopathic pulmonary fibrosis (IPF) by studying novel computational models where the epistatic effects (dominant, additive, recessive) of SNP-SNP interactions could be evaluated, and then compared the results with a previously published hypersensitivity pneumonitis (HP) study where the same novel models were used. Mexican Hispanic patients (IPF=84 & HP=75) and 194 healthy control individuals were evaluated. The goal was to identify SP SNPs and SNP-SNP interactions that associate with IPF as well as SNPs and interactions that may be unique to each of these interstitial diseases or common between them. We observed: 1) in terms of IPF, i) three single SFTPA1 SNPs to associate with decreased IPF risk, ii) three SFTPA1 haplotypes to associate with increased IPF risk, and iii) a number of three-SNP interactions to associate with IPF susceptibility. 2) Comparison of IPF and HP, i) three SFTPA1 and one SFTPB SNP associated with decreased risk in IPF but increased risk in HP, and one SFTPA1 SNP associated with decreased risk in both IPF and HP, ii) a number of three-SNP interactions with the same or different effect pattern associated with IPF and/or HP susceptibility, iii) one of the three-SNP interactions that involved SNPs of SFTPA1, SFTPA2, and SFTPD, with the same effect pattern, was associated with a disease-specific outcome, a decreased and increased risk in HP and IPF, respectively. This is the first study that compares the SP gene variants in these two phenotypically similar diseases. Our findings indicate that SNPs of all SFTPs may play an important role in the genetic susceptibility to IPF and HP. Importantly, IPF and HP share some SP genetic variants, suggesting common pathophysiological mechanisms and pathways regarding surfactant biogenesis, but also some differences, highlighting the diverse underlying pathogenic mechanisms between an inflammatory-driven fibrosis (HP) and an epithelial-driven fibrosis (IPF). Alternatively, the significant SNPs identified here, along with SNPs of other genes, could serve as markers to distinguish these two devastating diseases.

Dataset Information

SNP and Haplotype Interaction Models Reveal Association of Surfactant Protein Gene Polymorphisms With Hypersensitivity Pneumonitis of Mexican Population.

Publications

SNP and Haplotype Interaction Models Reveal Association of Surfactant Protein Gene Polymorphisms With Hypersensitivity Pneumonitis of Mexican Population.

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