TNF and LTA gene polymorphisms in cystic fibrosis patients: clinical parameters and inflammatory markers

The aim of the study was to investigate clinical parameters and inflammatory markers in cystic fibrosis patients (CF) with TNF and LTA gene polymorphisms: a G-to-A transition in position -308 in the promoter region of the TNF gene ( rs1800629 , TNF-308 ) and a A-to-G transition at position +252 in the first intron of the LTA gene (rs909253, LTA+252 ). The study included 120 children and 80 adults with CF. All patients had regularly (every 3-6 months) attended the Russian Pediatric Clinical Hospital or Pulmonology Research Institute for routine antibiotic therapy and clinical examination. The patients with genotype LTA+252AA (low production of lymphotoxin-alpha, LTa) were significantly older than those with genotypes LTA+252GG/AG (high LTa production). In the same time the groups did not differ significantly in term their pulmonary function test results, frequency of diabetes development, or number of died patients. However, in group with genotypes LTA+252GG/AG 5 of 6 patients with diabetes were below 14 years old. In contrast, there was only patient below 14 among 10 patients with diabetes from group with genotype LTA+252AA (р = 0,007). Patients with LTA+252GG/AG genotypes had elevated plasma levels of IL-17A и IFNg. The same trend was found in relation to plasma IL-8 concentrations. In conclusion, the children with genotypes LTA+252GG/AG had more often need of hospitalization and demonstrated increased rate of diabetes development. These phenomena may be partly explained by increased grade of systemic inflammation in the carriers of LTA+252G alleles. Further investigations with prolonged observation period and increased number of participants are needed to assess the risks of early diabetes development in CF patients with LTA+252 polymorphisms.

муковисцидоз, полиморфизм генов TNF, цитокины, сахарный диабет при муковисцидозе, фактор некроза опухолей-альфа, лимфотоксин-альфа, интерлейкин-17, интерферон-гамма, cystic fibrosis, TNF gene polymorphisms, cytokines, cystic fibrosis associated diabetes, tumor necrosis factor-alpha, lymphotoxin-alpha, interleukin-17, interferon-gamma

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