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TNF gene polymorphisms in cystic fibrosis patients: contribution to the disease progression

Galina Shmarina12, Alexander Pukhalsky1*, Nika Petrova3, Ekaterina Zakharova4, Lucine Avakian1, Nikolai Kapranov1 and Vladimir Alioshkin5

Author Affiliations

1 Department of Cystic Fibrosis, Research Centre for Medical Genetics, 1 Moskvorechie Street, Moscow, 115478, Russia

2 Laboratory of Cytokines, G. N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russia

3 Laboratory of Genetic Epidemiology, Research Centre for Medical Genetics, Moscow, Russia

4 Laboratory of Metabolic Diseases, Research Centre for Medical, Moscow, Russia

5 G. N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russia

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Journal of Translational Medicine 2013, 11:19  doi:10.1186/1479-5876-11-19

Published: 23 January 2013



It is well known that the disease progression in cystic fibrosis (CF) patients may be diverse in subjects with identical mutation in CFTR gene. It is quite possible that such heterogeneity is associated with TNF-α and/or LT-α gene polymorphisms since their products play a key role in inflammation. The aim of the study was to investigate the possible roles of TNF gene polymorphisms in CF disease phenotype and progression.


198 CF patients and 130 control subjects were genotyped for both TNF-α308GA and LT-α + 252AG polymorphisms.


The carriers of the TNF-α308A allele more frequently had asthma as compared to patients homozygous for the TNF-α308 G allele. In 9 of 108 (8.3%) of LTα + 252AA carriers, tuberculosis infection has been documented, whereas there was no case of tuberculosis among patients, either homozygous or heterozygous for LTα +252 G alleles (p = 0.01). We never observed virus hepatitis among LTα + 252GA carriers. The genotypes TNF-α308GGLT-α + 252AA and TNF-α308GALT-α + 252AG were unfavorable with regard to liver disease development (both p < 0.05). It was also shown that neutrophil elastase activity was higher in sputum specimens from high TNF producers with genotypes TNF-α308GA or LT-α + 252GG. In addition the carriers of such genotypes demonstrated a higher risk of osteoporosis development (p values were 0.011 and 0.017, respectively).


The carriers of genotypes, which are associated with higher TNF-α production, demonstrated increased frequency of asthma, higher levels of neutrophil elastase, and decrease of bone density. On the contrary, the carriers of genotypes associated with low TNF-α production showed a higher frequency of tuberculosis infection.

TNF; Gene polymorphism; Cystic fibrosis; Inflammation; Liver disease; Osteoporosis; Tuberculosis; Asthma