Lack of Association Between Toll-like Receptor 2 Polymorphisms (R753Q and A-16934T) and Atopic Dermatitis in Children from Thrace Region of Turkey

Abstract

Background:Atopic dermatitis is the most common chronic inflammatory skin disease. A complex interaction of both genetic and environmental factors is thought to contribute to the disease.Aims:To evaluate whether single nucleotide polymorphisms in the TLR2 gene c.2258C>T (R753Q) (rs5743708) and TLR2 c.-148+1614T>A (A-16934T) (rs4696480) (NM_0032643) are associated with atopic dermatitis in Turkish children.Study Design:Case-control study.Methods:The study was conducted on 70 Turkish children with atopic dermatitis aged 0.5-18 years. The clinical severity of atopic dermatitis was evaluated by the severity scoring of atopic dermatitis index. Serum total IgE levels, specific IgE antibodies to inhalant and food allergens were measured in both atopic dermatitis patients and controls, skin prick tests were done on 70 children with atopic dermatitis. Genotyping for TLR2 (R753Q and A-16934T) single nucleotide polymorphisms was performed in both atopic dermatitis patients and controls.Results:Cytosine-cytosine and cytosin-thymine genotype frequencies of the TLR2 R753Q single nucleotide polymorphism in the atopic dermatitis group were determined as being 98.6% and 1.4%, cytosine allele frequency for TLR2 R753Q single nucleotide polymorphism was determined as 99.29% and the thymine allele frequency was 0.71%, thymine-thymine, thymine-adenine, and adenine-adenine genotype frequencies of the TLR2 A-16934T single nucleotide polymorphism were 24.3%, 44.3%, and 31.4%. The thymine allele frequency for the TLR2 A-16934T single nucleotide polymorphism in the atopic dermatitis group was 46.43%, and the adenine allele frequency was 53.57%, respectively. There was not statistically significant difference between the groups for all investigated polymorphisms (p>0.05). For all single nucleotide polymorphisms studied, allelic distribution was analogous among atopic dermatitis patients and controls, and no significant statistical difference was observed. No homozygous carriers of the TLR2 R753Q single nucleotide polymorphism were found in the atopic dermatitis and control groups.Conclusion:The TLR2 (R753Q and A-16934T) single nucleotide polymorphisms are not associated with atopic dermatitis in a group of Turkish patients.

Langerhans and inflammatory dendritic epidermal cells in atopic dermatitis are tolerized toward TLR2 activation

“…Others showed an altered function of MyD88 signaling in mice macrophages bearing the TLR2 polymorphism R753Q . It has been reported that the frequency of R753Q is higher in AD children, while others showed a similar distribution in healthy children and concluded that the association between AD and R753Q is lacking . Nevertheless, it is unlikely that the polymorphisms are playing a major role in our data, as the prevalence of the R753Q polymorphism is around 10% …”

Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

“…The frequency of the R753Q in TLR2 was significantly higher in Italian AD children (16%) than in controls (6%), with a more severe phenotype [48]. However, there is a contrary report showing no correlation between the R753Q mutation in TLR2 and the severity of AD in children from Turkey [49]. The promoter polymorphism C-1237T in the TLR9 gene was associated with impaired immunity in some cases of AD [50].…”

Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review

“…Other genes involved in immune functions, such as IL2RA [13,76], IL4 and ADAM33 [84], TGFB1 [57], and MIF promoter [42] have also been significantly associated to increased risk of AD. The relationship of TLRs polymorphisms with AD, i.e., TLR2 rs55743708(G>A) and TLR4 rs4986790(A>G) were reported to increase levels of IL-4 and IL-10 in Russian AD patients [61], while other authors found no association of TLR2 polymorphisms, i.e., rs5743708 and rs4696480, in Turkish children with AD [69]. Also, significant SNPs in TSLP, a lymphopoietin, have been reported in Chinese Han [38], Korean [43], and American [62,71] patients.…”

“…On its behalf, most of the genes of the review associated to innate immune pathways (ADAM33, MIF, MMP9, ORM2, RETN, and TLR2) are related to neutrophil degranulation that contributes to the inflammation of the tissue in the AD [151,152]. In addition, a substantial number of publications [61,69,95,153] emphasize the importance of Toll-like receptor cascades on the development of AD and its link with other allergic diseases [154,155]. The TLR-2 rs4696480 polymorphism has also been associated with AD severity in adult patients in two different populations, and supported with functional studies [156,157].…”