Association of TLR-4 and TNF-alpha polymorphisms with clinical symptoms and cytokine levels in patients with allergic rhinitis

Abstract

Our objective was to determine the frequency of TNF-alpha -238, -308 G/A promoter and TLR-4 299 D/G and 399 T/I polymorphisms in healthy population and in patients with seasonal allergic rhinitis, and to examine its influences on serum TNF-alpha, TNF receptor-1, Fas, Fas-ligand, IgE levels and on clinical symptoms. A pilot study was performed in 66 patients with seasonal allergic rhinitis to ragweed pollen and 161 non-allergic subjects using PCR-RFLP technique and ELISA. Carriers of the -238A and -308G alleles have significantly higher TNF-alpha and IgE levels, clinical score values and lower peak nasal flow (PNIF) values during and after ragweed pollen season. Patients with the 299G/399I alleles of the TLR-4 gene have significantly lower TNF-alpha, Fas, FasL and IgE levels, clinical scores and higher PNIF values during and after pollen season. The -238A and -308G polymorphisms of the TNF-alpha promoter and 299D/399T polymorphisms of the TLR-4 gene are associated with more pronounced clinical symptoms, higher cytokine and IgE levels, and low PNIF values. These polymorphisms are very likely to contribute to the heterogeneity of clinical and laboratory parameters of patients.

Associations of TNFα <b><i>-308G>A</i></b>, TNFα <b><i>-238G>A</i></b>,<b> </b>IL-1α <b><i>-889C>T</i></b> and IL-10 <b><i>-1082G>A </i></b>Genetic Polymorphisms with Atopic Diseases: Asthma, Rhinitis and Dermatitis

“…However, there were very few carriers of this polymorphism (10 subjects), which limits the interpretation of the significance of this polymorphism in our study sample. Previous studies on the Caucasian population found that the TNFα -238G>A polymorphism was associated with an increased risk for asthma [22,40] and allergic rhinitis [41], while no significant association was found with atopic dermatitis [14,42,43]. …”

“…Therefore, it can be speculated that in atopic dermatitis a part of the pathogenesis is related to defective TNFα production and activity in the skin, which is promoted with the TNFα -308GG genotype. Additionally, the TNFα -308G>A polymorphism was found to be positively associated with serum TNFα levels, but negatively with nasal TNFα levels [34,41]. It will be of interest to further study the association of TNFα -308 genotypes with TNFα levels in the skin, respiratory mucosa and blood of atopic and nonatopic subjects, keeping in mind the already revealed discrepancy in the influence of TNFα polymorphisms on serum TNFα levels and local TNFα levels in nasal mucosa, as well as generally diminished TNFα levels in the immune cells of patients with atopic dermatitis [69,70,71,72].…”

“…Approximately half of the studies, including one genome-wide association study, claim no effect [17,18,19,20,21,22,23,24,25,26,27,28,29], while others argue for a significant association, either protective or predisposing [30,31,32,33,34,35,36,37,38,39,40]. Regarding atopic rhinitis and dermatitis, the association of TNFα -308 polymorphisms has rarely been studied [14,41,42,43]. Additionally, there are only a few studies regarding other selected polymorphisms and atopic diseases, also with conflicting results [14,22,29,40,41,42,43,44,45,46,47].…”

“…Regarding atopic rhinitis and dermatitis, the association of TNFα -308 polymorphisms has rarely been studied [14,41,42,43]. Additionally, there are only a few studies regarding other selected polymorphisms and atopic diseases, also with conflicting results [14,22,29,40,41,42,43,44,45,46,47]. Furthermore, confounding effects of lifestyle and environmental factors were rarely evaluated in studies assessing the association between genetic factors and atopic diseases.…”

Identification and Functional Characterization of Novel Genetic Variations in Porcine TLR5 Promoter

“…Thus, it has been observed that polymorphisms in human TLR promoters may result in deficiency in TLR signaling, increasing or decreasing the susceptibility to infectious disease (Ragnarsdóttir et al, 2010;Krasznai et al, 2011). In pigs, a total of 40 single-nucleotide polymorphisms (SNPs) have been reported in the TLR5 coding sequence (Yang et al, 2013).…”