Shared Enrichment of the MUC5B Variant rs35705950 in Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis: Evidence from a Russian Cohort

Background/Objectives: The MUC5B rs35705950 polymorphism is the strongest common genetic risk factor for idiopathic pulmonary fibrosis (IPF), whereas its role in fibrotic hypersensitivity pneumonitis (fHP) remains incompletely characterized, particularly in Eastern European cohorts. This study aimed to evaluate the distribution of MUC5B rs35705950 genotypes and alleles in Russian patients with IPF and fHP and to assess their association with disease susceptibility using a large external Russian reference dataset. Methods: The study included 114 patients with interstitial lung disease: 50 with IPF and 64 with fHP. Genotyping was performed using a custom PCR-restriction fragment length polymorphism assay. Genotype and allele frequencies were compared with an external reference dataset from the National Genetic Initiative of Russia (n = 89,261). Association analyses were performed under dominant T-carrier and allelic models. Results: The rs35705950 T allele was significantly enriched in both IPF and fHP compared with the external reference dataset. T-carrier genotypes were detected in 52.0% of patients with IPF and 42.2% of patients with fHP, compared with 18.9% in the reference dataset. T-allele frequencies were 28.0%, 26.6%, and 10.0%, respectively. In the dominant model, T-carrier status was associated with increased odds of IPF (OR = 4.65; 95% CI, 2.56–8.46; p < 0.001) and fHP (OR = 3.13; 95% CI, 1.83–5.29; p < 0.001). The direct comparison between IPF and fHP was inconclusive because of limited statistical power. Conclusions: In this Russian clinical cohort, the rs35705950 T allele was more frequent in patients with IPF and fHP than in the external Russian reference dataset. These findings provide regional replication of previously reported associations. The study did not assess causal mechanisms or diagnostic performance.