Analysis of MUC5B and tert gene variants in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a disease whose etiopathogenesis is not fully elucidated and it is thought that genetic and environmental factors play a role in the development of the disease. In our study, we aimed to determine the distribution characteristics of MUC5B and TERT alleles, their effects on the disease individually and together, and the relationship between the phenotypic and clinical characteristics of the patients with IPF. Methods: This study was performed on IPF patients and healthy control group admitted to the hospital between November 2018 and October 2019. IPF patients diagnosed with multidisciplinary councils meeting IPF diagnostic criteria in accordance with the 2018 ATS / ERS / JRS / ALAT Clinical Practice Guidelines were included in the case group. Patients with known cause of ILD and clinically significant disease other than IPF were excluded from the study. The control group consisted of individuals with no known malignancy, pulmonary disease and respiratory complaints without a diagnosis of IPF in the patient and his / her family. Demographic, clinical, physiological, radiological and pathological data of the cases were obtained during the examination or from the hospital electronic data recording system. Radiological classification of UIP was performed according to ATS / ERS / JRS / ALAT Clinical Practice Guide published in 2018. Genomic DNA was obtained from the peripheral blood samples by silica column method (Exgene Blood SV Mini, GeneAll, Korea). TERT (NC_000005.10: g.1286401C>A, NM_198253.2: c.1574-3777G>T, rs2736100) and MUC5B (NM_002458.2: c.-3133G>T, rs35705950) target variant regions were amplified by PCR method. Haplotype evaluation was performed by melt curve analysis of alleles-specific fluorescent probes. Quantitative PCR analysis was performed with LightCycler 480 II (Roche) instrument and LightCycler480 SW1.5 (Roche) program. Results: A total of 182 patients, 97 IPF patients and 85 control groups, were included in the study. 82 (84.5%) of the IPF patients were male and 15 (15.5%) were female. In the control group, 68 (80%) were male and 17 (20%) were female. The mean age of IPF patients was 67.6 ± 8.6 years and the control group was 67.5 ± 6.1 years. In our study, 5.2% of IPF patients were familial and 94.8% were sporadic. While 30.9% of IPF patients do not carry A risk allele, 69.1% were observed to have at least one risk allele. Whereas 35.3% of the control group did not carry A risk allele, 64.7% carried at least one risk allele. Although the A allele frequency was slightly increased in IPF cases compared to the control group, it was not statistically significant. In our study, a significant relationship was found between the MUC5B rs35705950 variant and IPF sensitivity in accordance with the literature. Compared to individuals with GG genotype; It was found that the risk of being ill was 7 times in patients carrying one risk allele and 10.5 times higher in patients carrying two risk alleles depending on the risk allele dose (respectively OR 7, 95 % CI 3.316-14.775, p<0.00; OR 10.5, 95 % CI 2,209-49,902, p<0.001). When the TERT and MUC5B gene are evaluated together; The group with a risk allele of 3-4 was found to have 14.545 times higher IPF risk than the group without any risk allele (OR 14.545, 95% CI 2,811-75,271, p=0.004). When the patients with IPF were classified as GG and GT + TT in terms of MUC5B genotypes, the mean age of diagnosis of the patients carrying at least one risk allele was 68, while the GG group was 62. Compared to the GG group, the age of diagnosis of the GT + TT group was found to be statistically significantly higher (p<0,05). Consistent with the literature, the mean FVC(%PRED) value was found to be statistically significantly higher in patients carrying two risk alleles (TT) for MUC5B than in those carrying 1 risk allele (GT) (p<0,05). Mean FEV1 / FVC (% PRED) value was found statistically significantly lower in this group (p<0,05). There was no significant relationship between basal physiological status, disease onset age, familial / sporadic status and TERT gene allele distributions of IPF patients. However, in the group that did not carry the A risk allele, the GAP score was found to be significantly higher than the group carrying this allele (p= 0,040). Conclusions: This study revealed a significant and strong correlation between MUC5B rs35705950 variant and IPF risk in accordance with the literature. In IPF cases in our society, it was determined that there was no difference in the distribution of variants of the TERT gene compared to the control group. In addition, there was no significant relationship between the TERT gene alleles and the phenotypic properties examined. Although our study has its limitations, it contributes to the literature especially in terms of creating the first data of Turkish society.