Photo Credit: Dr. Microbe

The following is a summary of “Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis,” published in the February 2024 issue of Pulmonology by Mota et al.

Hypersensitivity pneumonitis (HP) represents a complex interstitial lung disease with fibrotic phenotypes resembling idiopathic pulmonary fibrosis (IPF), particularly in genetically susceptible individuals. While various single nucleotide polymorphisms (SNPs) have been linked to IPF, the genetic underpinnings of fibrotic HP (fHP) remain elusive. This study explored the association between MUC5B and TOLLIP variants and their haplotypes with susceptibility, clinical manifestation, and survival among Portuguese fHP patients.

Conducting a case-control study involving 97 fHP cases and 112 controls, researchers analyzed six SNPs within the MUC5B and TOLLIP genes. Associations with fHP risk, survival, and clinical, radiographic, and pathological characteristics were investigated by comparing patients and controls.

The study group observed associations between MUC5B rs35705950 and three adjacent TOLLIP variants (rs3750920, rs111521887, and rs5743894) with increased susceptibility to fHP. Minor allele frequencies were notably higher among fHP patients compared to controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Additionally, haplotypes formed by these variants were linked to fHP susceptibility. Carriers of a specific haplotype (G-T-G-C) exhibited a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73–27.64, P = 0.006). Furthermore, associations were noted between TOLLIP rs111521887 and rs5743894 variants and reduced lung function at baseline, as well as the MUC5B SNP and radiographic features, highlighting the impact of genetic factors in fHP.

Their findings suggest that TOLLIP and MUC5B variants and haplotypes could be valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis. These genetic markers may aid in patient stratification and provide insights into the genetic determinants influencing the clinical trajectory of fHP.

Source: sciencedirect.com/science/article/pii/S2531043724000072