Associations of the <i>VDR</i> gene with clinical manifestations and complications of cystic fibrosis

Abstract

Cystic fibrosis (CF) is the most common severe autosomal recessive disease in the Caucasoid population caused by mutations in the CF transmembrane regulator (CFTR) gene. However, the course of the disease may be modulated by genetic factors other than the CFTR gene and may be pleiotropically influenced by VDR (Vitamin D Receptor) gene. The aim of the study was to search for associations between genetic variants (c.1206T&gt;C(A&gt;G), c.152T&gt;C, c.1174+283G&gt;A) of VDR gene and clinically significant manifestations of CF, complications, and responses to therapy. Methods. Patients with CF (n = 283) and healthy children (n = 333), who formed the control group, were examined. Calcidiol levels were tested in all subjects. Polymorphic variants of VDR gene (c.1206T&gt;C(A&gt;G), c.152T&gt;C, c.1174+283G&gt;A) were tested by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. It was found that carriers of the TT genotype of the c.152T&gt;C FokI variant of VDR gene are 6.3 times more likely to develop meconium ileus (odds ratio – OR – 6.375; p = 0.011), 3.2 times more likely – respiratory failure (OR – 3.253; p = 0.079), 3.4 times more likely – chronic lung infection (CIL) caused by Pseudomonas aeruginosa (OR – 3.432; p = 0.026), and 4 times more likely – CIL caused by non-fermenting gram-negative bacteria (OR – 4.056; p = 0.009). Carriers of the CC genotype of the c.1206T&gt;C(A&gt;G) TaqI genetic variant use systemic corticosteroids more frequently (66% vs 7%) (OR – 0.034; p = 0.001). It was shown that the AA genotype of the BsmlI polymorphism (c.1174 + 283G&gt;A) is 4 times more likely to be detected in children with CF-associated liver diseases (OR – 4.300; p = 0.051). Conclusion. The contribution of all studied genetic variants c.1206T&gt;C(A&gt;G) TaqI, c.152T&gt;C FokI, BsmlI (c.1174+283G&gt;A) of the VDR gene to the clinical manifestations, complications and response to therapy in CF is described.