Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Abstract

Background Psoriasis is a disease caused by genetics and immune system dysfunction, affecting the skin and joints. Toll-like receptors (TLRs) play an important role in triggering the innate immune response and controlling adaptive immunity. The role of TLR2 in the progression of psoriasis is not well understood. Methods A case-control study was conducted on a northern Chinese Han population, consisting of psoriasis patients and healthy control subjects. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls. Results Four TLR2 SNPs (rs11938228, rs4696480, rs3804099, rs5743699) were genotyped and found to be in linkage disequilibrium. The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model. The haplotypes ATTC and ATCC were found to be protective against psoriasis. Conclusion Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Keywords

Toll-like receptors 2 / psoriasis / polymorphism / susceptibility

References

[1] Griffiths C E, Barker J N. Pathogenesis and clinical features of Psoriasis. Lancet, 2007; 370(9583): 263-271. doi: 10.1016/S0140-6736(07)61128-3

[2] Yin X, Low H Q, Wang L, et al. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nat Commun, 2015; 6(1): 6916. doi: 10.1038/ncomms7916

[3] Grän F, Kerstan A, Serfling E, et al. Current developments in the immunology of psoriasis. Yale J Biol Med, 2020; 93(1): 97-110.

[4] Conrad C, Gilliet M. Psoriasis: from pathogenesis to targeted therapies. Clin Rev Allergy Immunol, 2018; 54(1): 102-113. doi: 10.1007/s12016-018-8668-1

[5] Miller L S. Toll-like receptors in skin. Adv Dermatol, 2008, 24: 71-87. doi: 10.1016/j.yadr.2008.09.004

[6] Chen J-Q, Szodoray P, Zeher M. Toll-Like receptor pathways in autoimmune diseases. Yale J Biol Med, 2016; 50(1): 1-17. doi: 10.1007/s12016-015-8473-z

[7] Ermertcan A T, Öztürk F, Gündüz K. Toll-like receptors and skin: TLRs and skin. Journal of the J Eur Acad Dermatol Venereol, 2011; 25(9): 997-1006. doi: 10.1111/j.1468-3083.2011.04049.x

[8] Marks K E, Cho K, Stickling C, et al. Toll-like receptor 2 in autoimmune inflammation. Immune Network, 2021; 21(3): e18. doi: 10.4110/in.2021.21.e18

[9] Garcia-Rodriguez S, Arias-Santiago S, Perandrés-López R, et al. Increased gene expression of Toll-like receptor 4 on peripheral blood mononuclear cells in patients with psoriasis: TLR4 up-regulation in psoriasis PBMC. J Eur Acad Dermatol Venereol, 2013; 27(2): 242-250. doi: 10.1111/j.1468-3083.2011.04372.x

[10] Carrasco S, Neves F S, Fonseca M H, et al. Toll-like Receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for a gram-positive inflammatory trigger? Clin Exp Rheumatol, 2011; 29(6): 958-962.

[11] Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2. A Genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Gene, 2010; 42(11): 985-990. doi: 10.1038/ng.694

[12] Stuart P E, Nair R P, Ellinghaus E, et al. Genome-wide association analysis identifies three psoriasis susceptibility Loci. Nat Gene, 2010, 42(11): 1000-1004. doi: 10.1038/ng.693

[13] Sun L D, Cheng H, Wang Z X, et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nate Gene, 2010; 42(11): 1005-1009. doi: 10.1038/ng.690

[14] Collaborative Association Study of Psoriasis (CASP), Genetic Analysis of Psoriasis Consortium, Psoriasis Association Genetics Extension, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate Immunity. Nat Gene, 2012; 44(12): 1341-1348. doi: 10.1038/ng.2467

[15] Shi G, Wang T, Li S, et al. TLR2 and TLR4 polymorphisms in Southern Chinese psoriasis vulgaris patients. J Dermatol Sci, 2016; 83(2): 145-147. doi: 10.1016/j.jdermsci.2016.04.014

[16] Sabah-Özcan S, Gürel G. The polymorphism rs4696480 in the TLR2 gene is associated with psoriasis patients in the Turkish Population. Immunol Let, 2019; 211: 28-32. doi: 10.1016/j.imlet.2019.05.008

[17] Gowin E, Świątek-Kościelna B, Kałużna E, et al. Analysis of TLR2, TLR4, and TLR9 single nucleotide polymorphisms in children with bacterial meningitis and their healthy family Members. Int J Infect Dis, 2017; 60: 23-28. doi: 10.1016/j.ijid.2017.04.024

[18] Zhou B, Liang S, Shang S, et al. Association of TLR2 and TLR9 gene polymorphisms with atopic dermatitis: a systematic review and meta-analysis with trial sequential Analysis. Immunol Med, 2023; 46(1): 32-44. doi: 10.1080/25785826.2022.2132683

[19] Loft N D, Skov L, Iversen L, et al. Associations between functional polymorphisms and response to biological treatment in Danish patients with Psoriasis. Pharmacogenomics J, 2018; 18(3): 494-500. doi: 10.1038/tpj.2017.31

[20] Lorenz E, Mira J P, Cornish K L, et al. A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun, 2000; 68(11): 6398-6401. doi: 10.1128/IAI.68.11.6398-6401.2000

[21] Zhou B, Liang S, Shang S, et al. Association of TLR2 and TLR9 gene polymorphisms with atopic dermatitis: a systematic review and meta-analysis with trial sequential Analysis. Immunol Med, 2022: 1-13.

[22] Potaczek D P, Przytulska-Szczerbik A, Bazan-Socha S, et al. Interaction between functional polymorphisms in FCER1A and TLR2 and the severity of atopic Dermatitis. Human Immunol, 2020; 81(12): 709-713. doi: 10.1016/j.humimm.2020.08.002

[23] Elloumi N, Tahri S, Fakhfakh R, et al. Role of innate immune receptors TLR4 and TLR2 polymorphisms in systemic lupus erythematosus Susceptibility. Ann Human Gene, 2022; 86(3): 137-144. doi: 10.1111/ahg.12458

[24] Zhang Y, Wang H C, Feng C, et al. Analysis of the association of polymorphisms rs 5743708 in TLR2 and rs4986790 in TLR4 with atopic dermatitis risk. Immunol Invest, 2019; 48(2): 169-180. doi: 10.1080/08820139.2018.1508228

[25] Zhang F, Gao X D, Wu W W, et al. Polymorphisms in Toll-like receptors 2, 4 and 5 are associated with legionella pneumophila Infection. Infection, 2013; 41(5): 941-948. doi: 10.1007/s15010-013-0444-9

[26] Shi G, Wang T, Li S, et al. TLR2 and TLR4 polymorphisms in Southern Chinese psoriasis vulgaris patients. J Dermatol Sci, 2016; 83(2): 145-147. doi: 10.1016/j.jdermsci.2016.04.014