Association of TLR2 Arg753Gln gene polymorphism with its expression level in nonagenarians with frailty

Abstract

TLR2 is an exceptional pattern-recognizing receptor because of its ability to heterodimerise with different types of TLRs, which allows it to recognize a wide range of molecular structures on the surface of pathogens. Polymorphisms in genes involved in the TLRs signaling cascade may be a factor in host susceptibility to the development of inflammation, affecting the outcome of a number of infectious diseases and immune diseases. The variant Arg753Gln (rs5743708) in the TLR2 gene is the most characterized missense mutation of the coding region in the TIR domain, which involves the substitution of arginine for glutamine at position 753 of the protein sequence. This functionally significant substitution leads to altered signaling and is associated with inflammatory responses. In this study, we investigated the association of the Arg753Gln (rs5743708) polymorphism of the TLR2 gene with the level of its expression in nonagenarians. The study included 82 nonagenarians. Frailty was detected in 41 subjects using a short physical performance battery, with registration in the test ≤ 7 points. It was shown that carriage of the Gln allele is statistically significantly associated with an increased risk of developing frailty; patients with the Arg/Gln genotype have a 12.8-fold higher chance of developing this geriatric syndrome. The Arg allele and the Arg/Arg genotype were found to be protective factors in the development of frailty in nonagenarians. Analysis of TLR2 gene expression in nonagenarians revealed a 2.79-fold increase in TLR2 expression relative to donors. Evaluation of TLR2 gene expression level in groups of nonagenarians with the presence and absence of frailty showed a 1.4-fold increase in TLR2 gene expression in nonagenarians with this geriatric syndrome. In patients with the Arg/Gln genotype, TLR2 gene expression was 1.3 times higher than in the group with the Arg/Arg genotype and 1.6 times higher than in the group with the Gln/Gln genotype. The increased frequency of occurrence of the Arg/Gln genotype of the Arg753Gln polymorphism of the TLR2 gene in nonagenarians with frailty may be due to increased gene expression of this receptor. It is necessary to conduct further functional and molecular genetic studies.