IL-17F gene polymorphisms in cystic fibrosis patients: influence on mortality rate

The aim of this study was to evaluate effects of IL-17F gene polymorphisms, rs2397084 (substitution of glutamic acid (GAG) for glycine (GGG) at position 126; Glu126Gly) and rs763780 (substitution of histidine (CAT) for arginine (CGT) at position 161; His161Arg) on the cystic fibrosis (CF) patients mortality rate. The study involved 82 patients who were regularly examined (every 3-6 months) and received antibiotic therapy. The frequency of IL-17F (rs2397084) A and G alleles was 90.2% and 9.8%, respectively. The frequency of IL-17F (rs763780) A and G alleles was 92.1% and 7.9%, respectively. The patients were divided into two groups. Group 1 included individuals with common AA-AA genotype (n=55). Group 2 included carriers of one or more minor G alleles (n=27). The patients of two groups did not differ in age, sex, or number of F508del mutation carriers. At the same time, there were 14 dead patients in group 1, whereas all patients from group 2 were alive. Thus, survival in groups 1 and 2 was 74.5% and 100%, respectively (p=0.0035, Fisher’s exact test). Analysis of the Kaplan-Meier curves showed that the overall survival of patients in the group 1 was significantly lower than the corresponding parameter in the group 2 (p=0.0026, Log-Rank Test). Repeated microbiological studies of sputum samples revealed a significant predominance of patients with chronic colonization of the Burkholderia cepacia complex (Bcc) in this group: 22 vs 1 patient in group 2 (χ2 = 11.82, p = 0.0006; OR 17.33 [95% CI 2.19-137.21]). Thus, increased mortality rate in CF patients with common AA-AA genotype is associated with a high incidence of chronic Bcc infection. Further investigations with increased number of participants are needed to estimate more accurately the true risks of Bcc infection and poor outcomes in CF patients with different IL-17F gene polymorphisms.

cystic fibrosis, IL-17F gene polymorphisms, Burkholderia cepacia complex, interleukin-17, cytokines

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