# IL1B gene variants, but not TNF, CXCL8, IL6 and IL10, modify the course of cystic fibrosis in Polish patients

## TL;DR

This study found that specific genetic variants in the IL1B gene are linked to more severe lung disease in Polish patients with cystic fibrosis.

## Contribution

The study identifies IL1B gene variants as potential predictors of severe lung disease in cystic fibrosis, not previously reported in this population.

## Key findings

- IL1B variants rs1143627 and rs16944 are more common in patients with severe lung disease.
- The IL1B haplotype AC is associated with a higher frequency in severe disease cases.
- TNF variant rs1800629 is less frequent in patients compared to healthy controls.

## Abstract

Background:
The main aim of this study was to evaluate whether selected polymorphic variants in genes from the inflammatory pathway can be predictors of pulmonary or digestive manifestation of cystic fibrosis, as well as of severity of lung disease.

Materials and methods:
Using pyrosequencing and sequencing we have genotyped 12 variants in
TNF (rs361525, rs1800629),
CXCL8 (rs4073, rs2227306, rs2227307, rs188378669),
IL1B (rs16944, rs1143634, rs1142639, rs1143627),
IL6 (rs1800795) and
IL10 (rs1800896) genes in a cohort of 55 Polish patients with diagnosed cystic fibrosis and controls. In our study group, a pulmonary manifestation of disease revealed 44 of subjects (80%), and digestive symptoms dominated in 11 (20%) of analyzed individuals. Severe lung dysfunction has occurred in 20 (36.4%) of patients.

Results:
We proved, that two promoter variants of
IL1B, rs1143627 (c.-118G > A) and rs16944 (c.-598T > C) are presented significantly more often in patients with severe character of lung disease compared to mild (82.5%
vs. 62.8%, p-value 0.030, and 87.5%
vs. 64.3%, p-value 0.008, respectively) in cystic fibrosis course. Haplotype AC formed by both changes had also a higher frequency (80%) in patients with severe course compared to the mild character (61.4%) of disease. However, the frequency of promoter variant
TNF c.-308C > T (rs1800629) was presented at a significantly lower level in the patient’s group compared to healthy controls (2.7%
vs. 15%, p-value 0.001). Furthermore, the presence of methicillin-resistant
Staphylococcus aureus significantly correlated with the lower FEV1% in patients (p-value 0.01).

Conclusions:
Genetic variants, rs1143627 and rs16944, of
IL1B are promising candidates as predictors of the severe character of lung disease in Polish patients with cystic fibrosis.