TLR通路基因多态性与变应性鼻炎的关联研究

doi:10.6040/j.issn.1673-3770.1.2019.008

Abstract

Abstract: Objective

The involvement of the Toll-like receptor (TLR) signaling pathway in allergic rhinitis (AR), asthma, and other allergic diseases is being intensively studied. The present study assessed the correlation between TLR pathway gene single nucleotide polymorphisms (SNPs) and incidence of AR, and investigated the influence of SNPs in the pathogenesis of AR.

Methods

Candidate TLR pathway SNPs were screened by a search of a bioinformatics database system using the TaqMan SNP genotyping system as part of a hospital-based case-control study of 452 AR patients and 491 healthy controls. Serum levels of eosinophil cationic protein, total IgE, and allergen-specific IgE were measured by the Immuno CAP blood test.

Results

Six SNPs were identified (TLR2 rs7656411, rs76112010, rs7682814 and CD14 rs2563298, rs2569190, rs2569191). Genotype frequencies of CD14 rs2563298 and rs2569191 were significantly different between the cases and controls (P<0.05). AR patients with asthma were significantly associated with the rs7656411, rs2563298, and rs2569191. Genotype frequencies of TLR2 rs7656411 were significantly different between controls and the male and history case subgroups. Significant differences were also found in genotypes of CD14 rs2563298 and rs2569191 compared with control and subgroups of cases. Gene interaction analysis revealed a three-locus interaction involving TLR2 rs7656411, CD14 rs2563298, and CD14 rs2569191 in AR cases.

Conclusion

Polymorphisms of TLR2 and CD14 in the TLR pathway may contribute to susceptibility of AR in this Chinese population.

Key words: Allergic rhinitis, Toll-like receptors, CD14, Single nucleotide polymorphism, Genetic association studies

CLC Number:

R765.21

Ruoxi CHEN,Qingzhao ZHANG,Meiping LU,Xinjie ZHU,Lei CHENG. Association of Toll-like receptor pathway gene polymorphisms with allergic rhinitis[J].Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 79-87.

Figures/Tables 6

Table 1

Table 2

Distribution of selected variables between cases and controls"

变量	病例组 (n = 452)	对照组 (n = 495)	P
年龄 (岁, $x ˉ ± s$ )	19.70 ± 12.60	20.10 ± 12.61	0.597^a
性别[n(%)]
男	302(66.8)	303(61.2)	0.073^a
女	150(33.2)	192(38.8)
鼻炎病程 (年, $x ˉ ± s$ )	6.62 ± 5.87
鼻腔总症状 ( $x ˉ ± s$ )	5.25 ± 2.39
血清总IgE [kU/L, M (IQR)]	264.0 (120.6~593.5)	26.8 (11.1~52.2)	< 0.001^b
特异性IgE [kU_A/L, M (IQR)]
屋尘螨	29.0(4.6~72.5)	—
粉尘螨	24.1 (5.0~69.9)	—
ECP [μg/L, median(IQR)]	12.7 (5.2~28.7)	4.6 (3.1~7.5)	< 0.001^b
伴随哮喘
是	118（26.1）
否	271（60.0）
家族史
是	122（27.0）
否	269（59.5）

Table 2

Table 3

Genotypes and allele frequencies of TLR2 and CD14 polymorphisms among cases and controls"

SNPs	基因型	病例组			对照组		Crude OR(95%CI)	Adjusted OR (95%CI)^a	P ^b
SNPs	基因型	n	%		n	%	Crude OR(95%CI)	Adjusted OR (95%CI)^a	P ^b
TLR2
rs7656411		n = 441			n =493
	GG	112	25.4		156	31.6	1.00 (reference)	1.00 (reference)	0.079
	GT	233	52.8		229	46.5	1.42 (1.05~1.92)	1.41 (1.04~1.91)
	TT	96	21.8		108	21.9	1.23 (0.86~1.79)	1.22 (0.84~1.76)
	GT/TT	329	74.6		337	68.4	1.36 (1.02~1.81)	1.35 (1.01~1.79)	0.035
	T allele	0.451							0.186
rs76112010		n = 446			n = 485
	GG	287	64.4		331	68.3	1.00 (reference)	1.00 (reference)	0.144
	GA	137	30.7		141	29.1	1.12 (0.84~1.49)	1.15 (0.86~1.53)
	AA	22	4.96		13	2.7	1.95 (0.97~3.95)	1.98 (0.98~4.02)
	GA/AA	159	35.7		154	31.2	1.19 (0.91~1.53)	1.22 (0.93~1.60)	0.209
	A allele	0.203							0.089
rs7682814		n = 441			n = 486
	GG	285		64.6	330	67.9	1.00 (reference)	1.00 (reference)	0.074
	GA	134		30.4	145	29.8	1.07 (0.81~1.42)	1.09 (0.82~1.45)
	AA	22		5.00	11	2.26	2.32 (1.10~4.86)	2.29 (1.09~4.81)
	GA/AA	42		15.9	38	13.9	1.15 (0.88~1.52)	1.17 (0.90~1.55)	0.292
	A allele	0.202							0.097
CD14
rs2563298		n = 434			n =479
	CC	336		77.4	326	68.1	1.00 (reference)	1.00 (reference)	0.003
	CA	89		20.5	131	27.3	0.66 (0.48~0.90)	0.65 (0.48~0.89)
	AA	9		2.1	22	4.60	0.40 (0.18~0.88)	0.40 (0.18~0.89)
	CA/AA	98		68.5	153	31.9	0.62 (0.46~0.84)	0.62 (0.46~0.83)	0.002
	A allele	0.123							<0.001
rs2569190		n = 450			n = 481
	AA	174		38.7	166	34.5	1.00 (reference)	1.00 (reference)	0.351
	AG	210		46.7	233	48.4	0.86 (0.65~1.14)	0.86 (0.64~1.15)
	GG	66		14.7	82	17.1	0.78 (0.88~1.92)	0.76 (0.52~1.94)
	AG/GG	276		61.3	315	65.5	0.84 (0.52~1.31)	0.84 (0.64~1.09)	0.188
	G allele	0.380							0.150
rs2569191		n = 441			n = 472
	CC	187		42.4	153	32.4	1.00 (reference)	1.00 (reference)	0.008
	CT	188		42.6	236	50.0	0.65 (0.49~0.87)	0.65 (0.48~0.87)
	TT	66		15.0	83	17.6	0.65 (0.44~0.96)	0.64 (0.44~0.95)
	CT/TT	254		57.6	319	67.6	0.65 (0.50~0.85)	0.65 (0.49~0.85)	0.002
	T allele	0.363							0.006

Table 3

Table 4

Table 5

Fig.1

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序号	SNPs	染色体位置	碱基变化	最小等位基因（MAF）			HWE P ^a
序号	SNPs	染色体位置	碱基变化	数据库	病例组	对照组	HWE P ^a
1	rs7656411	3′near gene	G/T	0.419	0.482	0.451	0.168
2	rs76112010	5′near gene	A/G	0.136	0.203	0.169	0.661
3	rs7682814	5′near gene	A/G	0.167	0.202	0.172	0.286
4	rs2563298	3′UTR	A/C	0.151	0.123	0.184	0.067
5	rs2569190	5′UTR	A/T	0.500	0.380	0.412	0.988
6	rs2569191	5′near gene	C/T	0.453	0.363	0.426	0.625

变量	分组	rs7656411 病例/对照		rs2563298 病例/对照		rs2569191 病例/对照
变量	分组	例数	Adjusted OR (95%CI)^b	例数	Adjusted OR (95%CI)^b	例数	Adjusted OR (95%CI)^b
年龄(岁)	<18	247/239	1.33(0.88~1.99)	244/239	0.54(0.36~0.80)	247/236	0.65(0.44~0.94)
	≥18	194/254	1.36(0.91~2.06)	191/240	0.73(0.47~1.13)	194/236	0.66(0.44~0.98)
性别	男	295/303	1.60(1.12~2.30)	289/296	0.75(0.52~1.07)	293/289	0.66(0.47~0.93)
	女	146/190	0.97(0.60~1.57)	146/183	0.42(0.25~0.72)	148/183	0.62(0.40~0.98)
哮喘	无	263/493	1.28(0.81~2.03)	261/479	0.45(0.27~0.75)	262/472	0.53(0.35~0.81)
	有	116/493	1.61(1.13~2.28)	115/479	0.60(0.42~0.85)	116/472	0.70(0.51~0.96)
家族史	无	120/493	1.20(0.76~1.89)	118/479	0.56(0.35~0.92)	120/472	0.85(0.56~1.31)
	有	260/493	1.64(1.16~2.33)	260/479	0.55(0.38~0.79)	260/472	0.57(0.42~0.78)
VAS	<5	247/493	1.25(0.88~1.77)	241/479	0.65(0.45~0.92)	246/472	0.72(0.52~0.99)
	≥5	194/493	1.45(0.99~2.12)	193/479	0.60(0.40~0.88)	195/472	0.57(0.41~0.80)
IgE ^a	低	135/493	1.41(0.99~2.00)	234/479	0.45(0.31~0.67)	237/472	0.61(0.44~0.84)
	高	206/493	1.31(0.90~1.89)	200/479	0.82(0.57~1.19)	204/472	0.71(0.50~0.99)

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Association of Toll-like receptor pathway gene polymorphisms with allergic rhinitis

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