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)

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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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