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

Siyu Hao; Yu Zhang; Anqi Yin; Ying Lyu; Nannan Tong; Jiangtian Tian; Yuzhen Li

doi:10.1515/fzm-2024-0010

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

doi: 10.1515/fzm-2024-0010

Siyu Hao^{1, #},
Yu Zhang^{1, #},
Anqi Yin¹,
Ying Lyu¹,
Nannan Tong¹,
Jiangtian Tian^{2, 3
, ,},
Yuzhen Li^{1
, ,}

1.
Department of Dermatology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China
2.
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150000, China
3.
Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China

Funds:

grants from the National Natural Science Foundation of China 82304000

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Corresponding author: Jiangtian Tian, tianjiangtian@126.com; Yuzhen Li, lyzdermatology@163.com

摘要

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.
- Toll-like receptors 2 /
- psoriasis /
- polymorphism /
- susceptibility

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Figure 1. Linkage disequilibrium analyses

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Table 1. Sequence of primers

Primer position	Primer sequence (5'-3')
s11938228
Forward primer	GGGGCAAGAATAACCAAGACACA
Reverse primer	GACATGCCCATATAGGGGTAGATCTTG
rs4696480
Forward primer	GGTTCTGGAGTCTGGGAAGTCCA
Reverse primer	ACTGCGAGCTGAGAGGTGGAAC
rs3804099
Forward primer	TGCAAATCCTGAGAGTGGGAAAT
Reverse primer	TCCAAACATTCCACGGAACTTG
rs5743699
Forward primer	AGGATGCCTGGCCCTCTCTACA
Reverse primer	TGTCTTGGGAATGCAGCCTGTT

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Table 2. iMLDR probe sequences

SNP allele	Primer sequence (5'-3')	LDR product
s11938228_modify	TCTATCCCTATACCAGCAACACACTATATTAAATTTTTTTTTTT	63.21
s11938228_C	TTCCGCGTTCGGACTGATATTCAGTGCTATTCTGATCCAATGTTCATGTG	67.77
s11938228_A	TACGGTTATTCGGGCTCCTGTTCAGTGCTATTCTGATCCAATGTTCATGTT	66.56
rs4696480_modify	GAGGGTCATCTGGCTACATTATAACATGTTTTTTTTTT	63.95
rs4696480_A	TCTCTCGGGTCAATTCGTCCTTCAAGATTGAAGGGCTGCATCTCGA	68.65
rs4696480_T	TGTTCGTGGGCCGGATTAGTCAAGATTGAAGGGCTGCATCTCGT	67.70
rs3804099_modify	GTAAGTCATCTGATCCTTCATATGAAGCATTTTTTTTT	63.00
rs3804099_C	TTCCGCGTTCGGACTGATATGAGCCAAAAAGTTTGAAGTCAATTCAGTAC	66.86
rs3804099_T	TACGGTTATTCGGGCTCCTGTGAGCCAAAAAGTTTGAAGTCAATTCAGCAT	66.40
rs5743699_modify	TGAGCAAAGTCTCTCCGGTTTTTTTTTTTTTT	63.53
rs5743699_C	TCTCTCGGGTCAATTCGTCCTTTCTTACTGATATCAATGTTAGTCAAGTTTTTCACAG	64.81
rs5743699_T	TGTTCGTGGGCCGGATTAGT TCTTACTGATATCAATGTTAGTCAAGTTTTTCACAA	65.02

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Table 3. Demographic characteristics of the studied population

Characteristic	Cases, (N = 270)	Controls, (N = 247)	P
Gender, N (%)
Male	166 (61.5)	142 (57.5)	0.3706
Female	104 (38.5)	105 (42.5)
Age, years	38.17 ± 9.90	37.94 ± 9.70	0.7890
PASI, N (%)
≤ 10	223 (82.6)	-	-
> 10	47 (17.4)	-	-
Age at onset, N (%)
≤ 40 years	219 (81.1)	-	-
> 40 years	51 (18.9)	-	-
Family history, N (%)
Yes	102 (37.8)	-	-
No	168 (62.2)	-	-
Data were presented as N(%).

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Table 4. Allele and genotype frequencies of TLR2 SNPs in the case and control groups

SNP	Model		Controls	Cases	OR (95% CI)	P	P^*	OR (95% CI)	P^#
rs11938228	Codominant	C/C	56 (22.7)	91 (33.7)	1.00	0.00180	0.0072	1.00	0.0016
		C/A	124 (50.2)	135 (50.0)	0.67 (0.44-1.01)			0.66 (0.43-1.00)
		A/A	67 (27.1)	44 (16.3)	0.40 (0.24-0.67)			0.40 (0.24-0.66)
		C	236 (47.8)	317 (58.7)	1.00	0.00054	0.0022
		A	258 (52.2)	223 (41.3)	0.64 (0.50-0.82)
	Dominant	C/C	56 (22.7)	91 (33.7)	1.00	0.00530	0.0212	1.00	0.0041
		C/A-A/A	191 (77.3)	179 (66.3)	0.58 (0.39-0.85)			0.57 (0.38-0.84)
	Recessive	C/C-C/A	180 (72.9)	226 (83.7)	1.00	0.00270	0.0108	1.00	0.0027
		A/A	67 (27.1)	44 (16.3)	0.52 (0.34-0.80)			0.52 (0.34-0.80)
	Overdominant	C/C-A/A	123 (49.8)	135 (50.0)	1.00	0.96000	1.00	1.00	0.9100
		C/A	124 (50.2)	135 (50.0)	0.99 (0.70-1.40)			0.98 (0.69-1.39)
rs4696480	Codominant	A/A	57 (23.1)	87 (32.2)	1.00	0.01300	0.052	1.00	0.0120
		A/T	125 (50.6)	136 (50.4)	0.71 (0.47-1.08)			0.70 (0.46-1.06)
		T/T	65 (26.3)	47 (17.4)	0.47 (0.29-0.78)			0.47 (0.28-0.78)
		A	239 (48.4)	310 (57.4)	1.00	0.00400	0.016
		T	255 (51.6)	230 (42.6)	0.70(0.54-0.89)
	Dominant	A/A	57 (23.1)	87 (32.2)	1.00	0.02000	0.08	1.00	0.0170
		A/T-T/T	190 (76.9)	183 (67.8)	0.63 (0.43-0.93)			0.62 (0.42-0.92)
	Recessive	A/A-A/T	182 (73.7)	223 (82.6)	1.00	0.01400	0.056	1.00	0.0150
		T/T	65 (26.3)	47 (17.4)	0.59 (0.39-0.90)			0.59 (0.39-0.91)
	Overdominant	A/A-T/T	122 (49.4)	134 (49.6)	1.00	0.96000	1.00	1.00	0.9000
		A/T	125 (50.6)	136 (50.4)	0.99 (0.70-1.40)			0.98 (0.69-1.38)
rs3804099	Codominant	T/T	123 (49.8)	121 (44.8)	1.00	0.52000	1.00	1.00	0.5300
		C/T	106 (42.9)	127 (47.0)	1.22 (0.85-1.75)			1.21 (0.85-1.74)
		C/C	18 (7.3)	22 (8.2)	1.24 (0.63-2.43)			1.26 (0.64-2.46)
		T	352 (71.3)	369 (68.3)	1.00	0.30700	1.00
		C	142 (28.7)	171 (31.7)	1.15 (0.88-1.50)
	Dominant	T/T	123 (49.8)	121 (44.8)	1.00	0.26000	1.00	1.00	0.2600
		C/T-C/C	124 (50.2)	149 (55.2)	1.22 (0.86-1.73)			1.22 (0.86-1.72)
	Recessive	T/T-C/T	229 (92.7)	248 (91.8)	1.00	0.71000	1.00	1.00	0.6800
		C/C	18 (7.3)	22 (8.2)	1.13 (0.59-2.16)			1.15 (0.60-2.19)
	Overdominant	T/T-C/C	141 (57.1)	143 (53.0)	1.00	0.35000	1.00	1.00	0.3600
rs5743699		C/T	106 (42.9)	127 (47.0)	1.18 (0.83-1.67)			1.18 (0.83-1.67)
		C/C	245 (99.2)	268 (99.3)	1.00	0.93000	1.00	1.00	0.8600
		C/T	2 (0.8)	2 (0.7)	0.91 (0.13-6.54)			0.84 (0.12-6.05)
		C	492 (99.6)	538 (99.6)	1.00	0.93000	1.00
		T	2 (0.4)	2 (0.4)	0.91 (0.13-6.54)
Data were presented as N(%). P: model-based statistical P value, P^*: P value adjusted Bonferroni correction, P^#: P value adjusted by age and sex; OR: odds ratio; 95% CI: 95% confidence interval.

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Table 5. Haplotype association with psoriasis

	rs11938228	rs4696480	rs3804099	rs5743699	Total	Frequency in control	Frequency in cases	OR (95% CI)		P	P^*	OR (95% CI)		P^#
1	A	T	T	C	0.44	0.48	0.40	0.713	(0.557-0.912)	0.007	0.113	0.705	(0.551-0.902)	0.005
2	C	A	C	C	0.28	0.25	0.30	1.262	(0.960-1.661)	0.095	1.000	1.236	(0.941-1.623)	0.126
3	C	A	T	C	0.24	0.21	0.26	1.299	(0.974-1.732)	0.075	1.000	1.328	(0.994-1.775)	0.054
4	A	T	C	C	0.01	0.02	0.01	0.248	(0.067-0.916)	0.024	0.383	0.225	(0.047-1.068)	0.04
5	C	T	T	C	0.01	0.01	0.01	2.512	(0.623-10.133)	0.180	1.000	2.461	(0.649-9.329)	0.171
6	A	A	T	C	0.01	0.01	0.01	1.289	(0.334-4.975)	0.711	1.000	1.144	(0.305-4.287)	0.84
7	C	T	C	C	0.01	0	0.01	1.836	(0.382-8.831)	0.441	1.000	1.835	(0.334-10.067)	0.477
9	A	T	T	T	0	0	0	0.027	(0.001-0.507)	0.267	1.000	-		-
P*: P value after Bonferroni correction; P^#: the OR and P values were adjusted for age and sex.

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Table 6. Analysis of linkage disequilibrium based on evaluation of D' in patients

	rs11938228	rs4696480	rs3804099	rs5743699
rs11938228	-	0.948	0.869	0.961
rs4696480	-	-	0.852	0.956
rs3804099	-	-	-	0.449
rs5743699	-	-	-	-

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Table 7. Analysis of linkage disequilibrium based on R² statistics in patients

	rs11938228	rs4696480	rs3804099	rs5743699
rs11938228	-	0.885	0.285	0.004
rs4696480	-	-	0.278	0.004
rs3804099	-	-	-	0
rs5743699	-	-	-	-

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参考文献(26)

[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 rs5743708 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

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

doi: 10.1515/fzm-2024-0010

Corresponding author: Jiangtian Tian, tianjiangtian@126.com; Yuzhen Li, lyzdermatology@163.com

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

doi: 10.1515/fzm-2024-0010

Corresponding author: Jiangtian Tian, tianjiangtian@126.com; Yuzhen Li, lyzdermatology@163.com

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