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. 2023 Jun 28;24(13):10748.
doi: 10.3390/ijms241310748.

The Presence of T Allele (rs35705950) of the MUC5B Gene Predicts Lower Baseline Forced Vital Capacity and Its Subsequent Decline in Patients with Hypersensitivity Pneumonitis

Katarzyna B Lewandowska  1 , Monika Szturmowicz  1 , Urszula Lechowicz  2 , Monika Franczuk  3 , Katarzyna Błasińska  4 , Maria Falis  1 , Kamila Błaszczyk  1 , Małgorzata Sobiecka  1 , Dorota Wyrostkiewicz  1 , Izabela Siemion-Szcześniak  1 , Małgorzata Bartosiewicz  1 , Piotr Radwan-Röhrenschef  1 , Adriana Roży  2 , Joanna Chorostowska-Wynimko  2 , Witold Z Tomkowski  1
Affiliations

The Presence of T Allele (rs35705950) of the MUC5B Gene Predicts Lower Baseline Forced Vital Capacity and Its Subsequent Decline in Patients with Hypersensitivity Pneumonitis

Katarzyna B Lewandowska et al. Int J Mol Sci. .

Abstract

Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes-fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment.

Keywords: MUC5B polymorphism; disease progression; hypersensitivity pneumonitis; response to treatment.

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Conflict of interest statement

K.B.L. received a fee for lectures from Boehringer Ingelheim and Roche, and travel grants for international conferences from Boehringer Ingelheim and Roche. M.S. (Monika Szturmowicz), M.S. (Małgorzata Sobiecka), P.R.-R., and W.Z.T. received a fee for lectures from Boehringer Ingelheim. The remaining authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Probability of FVC%pred decline during observation according to MUC5B status. FVC—forced vital capacity, GG—GG genotype, GT/TT—GT/TT genotype.
See this image and copyright information in PMC

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