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

References 58

1	Bousquet J , Khaltaev N , Cruz AA , et al . Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)[J]. Allergy, 2008, 63(Suppl 86): 8-160. doi:10.1111/j.1398-9995.2007.01620.x . doi: 10.1111/j.1398-9995.2007.01620.x
2	Zhang L , Han DM , Huang D , et al . Prevalence of self-reported allergic rhinitis in eleven major cities in china[J]. Int Arch Allergy Immunol, 2009, 149(1): 47-57. doi:10.1159/000176306 . doi: 10.1159/000176306
3	Linneberg A , Henrik Nielsen N , Frølund L , et al . The link between allergic rhinitis and allergic asthma: a prospective population-based study. The copenhagen allergy study[J]. Allergy, 2002, 57(11): 1048-1052. doi: 10.1034/j.1398-9995.2002.23664.x doi: 10.1034/j.1398-9995.2002.23664.x
4	Bugiani M , Carosso A , Migliore E , et al . Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy[J]. Allergy, 2005, 60(2): 165-170. doi:10.1111/j.1398-9995.2005.00659.x . doi: 10.1111/j.1398-9995.2005.00659.x
5	Leynaert B , Neukirch F , Demoly P , et al . Epidemiologic evidence for asthma and rhinitis comorbidity[J]. J Allergy Clin Immunol, 2000, 106(5 Suppl): S201-S205. doi: 10.1067/mai.2000.110151 . doi: 10.1067/mai.2000.110151
6	Cookson W . The alliance of genes and environment in asthma and allergy[J]. Nature, 1999, 402(6760 Suppl): B5-11. doi: 10.1038/35037002 . doi: 10.1038/35037002
7	Barnes KC . Evidence for common genetic elements in allergic disease[J]. J Allergy Clin Immunol, 2000, 106(5 Suppl): S192-S200. doi: 10.1067/mai.2000.110150 . doi: 10.1067/mai.2000.110150
8	Grossman J . One airway, one disease[J]. Chest, 1997, 111(2 Suppl): 11S-16S. PMID: 9042022.
9	Zarember KA , Godowski PJ . Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines[J]. J Immunol, 2002, 168(2): 554-561. doi: 10.4049/jimmunol.169.2.1136 . doi: 10.4049/jimmunol.169.2.1136
10	Chuang TH , Ulevitch RJ . Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9[J]. Eur Cytokine Netw, 2000, 11(3): 372-378. doi:10.1093/embo-reports/kvd058 . doi: 10.1093/embo-reports/kvd058
11	Zhou C , Kang XD , Chen Z . A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen[J]. J Zhejiang Univ Sci B, 2008, 9(4): 279-285. doi:10.1631/jzus.B0730029 . doi: 10.1631/jzus.B0730029
12	Patel M , Xu DM , Kewin P , et al . TLR2 agonist ameliorates established allergic airway inflammation by promoting Th₁ response and not via regulatory T cells[J]. J Immunol, 2005, 174(12): 7558-7563. doi: 10.4049/jimmunol.174.12.7558 . doi: 10.4049/jimmunol.174.12.7558
13	Liu CF , Drocourt D , Puzo G , et al . Innate immune response of alveolar macrophage to house dust mite allergen is mediated through TLR2/-4 co-activation[J]. PLoS One, 2013, 8(10): e75983. doi:10.1371/journal.pone. 0075983 . doi: 10.1371/journal.pone. 0075983
14	Crellin NK , Garcia RV , Hadisfar O , et al . Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP₃ in CD4+CD25+ T regulatory cells[J]. J Immunol, 2005, 175(12): 8051-8059. doi: 10.4049/jimmunol.175.12.8051 . doi: 10.4049/jimmunol.175.12.8051
15	Xu DM , Liu HY , Komai-Koma M . Direct and indirect role of Toll-like receptors in T cell mediated immunity[J]. Cell Mol Immunol, 2004, 1(4): 239-246. PMID: 16225766.
16	Xirakia C , Koltsida O , Stavropoulos A , et al . Toll-like receptor 7-triggered immune response in the lung mediates acute and long-lasting suppression of experimental asthma[J]. Am J Respir Crit Care Med, 2010, 181(11): 1207-1216. doi:10.1164/rccm.200908-1255OC . doi: 10.1164/rccm.200908-1255OC
17	Serebrisky D , Teper AA , Huang CK , et al . CpG oligodeoxynucleotides can reverse Th₂-associated allergic airway responses and alter the B_7.1/B_7.2 expression in a murine model of asthma[J]. J Immunol, 2000, 165(10): 5906-5912. doi:10.4049/jimmunol.165.10.5906 . doi: 10.4049/jimmunol.165.10.5906
18	Rhee CS , Libet L , Chisholm D , et al . Allergen-independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis[J]. Immunology, 2004, 113(1): 106-113. doi:10.1111/j.1365-2567. 2004.01930.x . doi: 10.1111/j.1365-2567. 2004.01930.x
19	Narayanan KB , Park HH . Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways[J]. Apoptosis, 2015, 20(2): 196-209. doi:10.1007/s10495-014-1073-1 . doi: 10.1007/s10495-014-1073-1
20	Qiao H , Andrade MV , Lisboa FA , et al . FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells[J]. Blood, 2006, 107(2): 610-618. doi:10.1182/blood-2005-06-2271 . doi: 10.1182/blood-2005-06-2271
21	Nigo YI, Yamashita M , Hirahara K , et al . Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function[J]. Proc Natl Acad Sci USA, 2006, 103(7): 2286-2291. doi:10.1073/pnas.0510685103 . doi: 10.1073/pnas.0510685103
22	Compton T , Kurt-Jones EA , Boehme KW , et al . Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2[J]. J Virol, 2003, 77(8): 4588-4596. doi: 10.1128/jvi.77.8.4588-4596.2003 . doi: 10.1128/jvi.77.8.4588-4596.2003
23	Kormann MS , Depner M , Hartl D , et al . Toll-like receptor heterodimer variants protect from childhood asthma[J]. J Allergy Clin Immunol, 2008, 122(1): 86-92, 92.e1-8. doi:10.1016/j.jaci.2008.04.039 . doi: 10.1016/j.jaci.2008.04.039
24	Qian FH , Zhang Q , Zhou LF , et al . Polymorphisms in the toll-like receptor 2 subfamily and risk of asthma: a case-control analysis in a Chinese population[J]. J Invest Allergol Clin Immunol, 2010, 20(4): 340-346. doi: 10.1089/jir.2009.0014 . doi: 10.1089/jir.2009.0014
25	Noguchi E , Nishimura F , Fukai H , et al . An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population[J]. Clin Exp Allergy, 2004, 34(2): 177-183. doi: 10.1111/j.1365-2222.2004.01839.x . doi: 10.1111/j.1365-2222.2004.01839.x
26	Møller-Larsen S , Nyegaard M , Haagerup A , et al . Association analysis identifies TLR7 and TLR8 as novel risk genes in asthma and related disorders[J]. Thorax, 2008, 63(12): 1064-1069. doi:10.1136/thx.2007.094128 . doi: 10.1136/thx.2007.094128
27	Smit LA , Siroux V , Bouzigon E , et al . CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults[J]. Am J Respir Crit Care Med, 2009, 179(5): 363-368. doi:10.1164/rccm.200810-1533OC . doi: 10.1164/rccm.200810-1533OC
28	Tewfik MA , Bossé Y , Lemire M , et al . Polymorphisms in interleukin-1 receptor-associated kinase 4 are associated with total serum IgE[J]. Allergy, 2009, 64(5): 746-753. doi:10.1111/j.1398-9995.2008.01889.x . doi: 10.1111/j.1398-9995.2008.01889.x
29	Savenije OE , Mahachie John JM , Granell R , et al . Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood[J]. J Allergy Clin Immunol, 2014, 134(1): 170-177. doi:10.1016/j.jaci.2013.12.1080 . doi: 10.1016/j.jaci.2013.12.1080
30	Kang I , Oh YK , Lee SH , et al . Identification of polymorphisms in the Toll-like receptor gene and the association with allergic rhinitis[J]. Eur Arch Otorhinolaryngol, 2010, 267(3): 385-389. doi:10.1007/s00405-009-1100-y . doi: 10.1007/s00405-009-1100-y
31	Senthilselvan A , Rennie D , Chénard L , et al . Association of polymorphisms of toll-like receptor 4 with a reduced prevalence of hay fever and atopy[J]. Ann Allergy Asthma Immunol, 2008, 100(5): 463-468. doi:10.1016/S1081-1206(10)60472-3 . doi: 10.1016/S1081-1206(10)60472-3
32	Nilsson D , Andiappan AK , Halldén C , et al . Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study[J]. BMC Med Genet, 2012, 13: 66. doi:10.1186/1471-2350-13-66 . doi: 10.1186/1471-2350-13-66
33	Liang XH , Cheung W , Heng CK , et al . Absence of the toll-like receptor 4 gene polymorphisms Asp299Gly and Thr399Ile in Singaporean Chinese[J]. Ther Clin Risk Manag, 2005, 1(3): 243-246. PMID: 18360565.
34	Bousquet PJ , Combescure C , Neukirch F , et al . Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines[J]. Allergy, 2007, 62(4): 367-372. doi:10.1111/j.1398-9995.2006.01276.x . doi: 10.1111/j.1398-9995.2006.01276.x
35	Basu S , Fenton MJ . Toll-like receptors: function and roles in lung disease[J]. Am J Physiol Lung Cell Mol Physiol, 2004, 286(5): L887-L892. doi:10.1152/ajplung.00323.2003 . doi: 10.1152/ajplung.00323.2003
36	Velasco G , Campo M , Manrique OJ , et al . Toll-like receptor 4 or 2 agonists decrease allergic inflammation[J]. Am J Respir Cell Mol Biol, 2005, 32(3): 218-224. doi:10.1165/rcmb.2003-0435OC . doi: 10.1165/rcmb.2003-0435OC
37	Redecke V , Häcker H , Datta SK , et al . Cutting edge: activation of Toll-like receptor 2 induces a Th₂ immune response and promotes experimental asthma[J]. J Immunol, 2004, 172(5): 2739-2743. doi: https://doi.org/10.4049/jimmunol.172.5.2739 . doi: 10.4049/jimmunol.172.5.2739
38	Fuertes E , Brauer M , MacIntyre E , et al . Childhood allergic rhinitis, traffic-related air pollution, and variability in the GSTP₁, TNF, TLR2, and TLR4 genes: results from the TAG Study[J]. J Allergy Clin Immunol, 2013, 132(2): 342-352.e2. doi:10.1016/j.jaci.2013.03.007 . doi: 10.1016/j.jaci.2013.03.007
39	Smit LA , Siroux V , Bouzigon E , et al . CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults[J]. Am J Respir Crit Care Med, 2009, 179(5): 363-368. doi:10.1164/rccm.200810-1533OC . doi: 10.1164/rccm.200810-1533OC
40	Smit LA , Bongers SI, Ruven HJ , et al . Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study[J]. Clin Exp Allergy, 2007, 37(11): 1602-1608. doi:10.1111/j.1365-2222.2007.02831.x . doi: 10.1111/j.1365-2222.2007.02831.x
41	Lachheb J , Dhifallah IB , Chelbi H , et al . Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children[J]. Tissue Antigens, 2008, 71(5): 417-425. doi:10.1111/j.1399-0039.2008.01011.x . doi: 10.1111/j.1399-0039.2008.01011.x
42	Hussein YM , Awad HA , Shalaby SM , et al . Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to asthma and allergic rhinitis: a case-control analysis[J]. Cell Immunol, 2012, 274(1/2): 34-38. doi:10.1016/j.cellimm.2012.02.006 . doi: 10.1016/j.cellimm.2012.02.006
43	Ortiz-Martínez MG , Frías-Belén O , Nazario-Jiménez S , et al . A case-control study of innate immunity pathway gene polymorphisms in Puerto Ricans reveals association of toll-like receptor 2 +596 variant with asthma[J]. BMC Pulm Med, 2016, 16(1): 112. doi:10.1186/s12890-016-0272-7 . doi: 10.1186/s12890-016-0272-7
44	Gao YF , Xiao HY , Wang YB , et al . Association of single-nucleotide polymorphisms in toll-like receptor 2 gene with asthma susceptibility: a meta-analysis[J]. Medicine (Baltimore), 2017, 96(20): e6822. doi:10.1097/MD. 0000-000000006822 . doi: 10.1097/MD. 0000-000000006822
45	Nabih ES , Kamel HF , Kamel TB . Association between CD14 polymorphism (-1145G/A) and childhood bronchial asthma[J]. Biochem Genet, 2016, 54(1): 50-60. doi:10.1007/s10528-015-9699-4 . doi: 10.1007/s10528-015-9699-4
46	Micheal S , Minhas K , Ishaque M , et al . Promoter polymorphisms of the CD14 gene are associated with atopy in Pakistani adults[J]. J Invest Allergy Clin Immunol, 2011, 21(5): 394-397. doi: 10.1080/09593330902990089 . doi: 10.1080/09593330902990089
47	Penders J , Thijs C , Mommers M , et al . Host-microbial interactions in childhood atopy: toll-like receptor 4 (TLR4), CD14, and fecal Escherichia coli[J]. J Allergy Clin Immunol, 2010, 125(1): 231-236.e1-5. doi:10.1016/j.jaci. 2009. 10.011 . doi: 10.1016/j.jaci. 2009. 10.011
48	Takeuchi K , Suzuki S , Yagawa M , et al . A CD14 gene polymorphism is associated with the IgE level for Dermatophagoides pteronyssinus[J]. Acta Otolaryngol, 2005, 125(9): 966-971. doi:10.1080/00016480510044197 . doi: 10.1080/00016480510044197
49	Chen ML , Zhao H , Huang QP , et al . Single nucleotide polymorphisms of IL-13 and CD14 genes in allergic rhinitis: a meta-analysis[J]. Eur Arch Otorhinolaryngol, 2018, 275(6): 1491-1500. doi:10.1007/s00405-018-4975-7 . doi: 10.1007/s00405-018-4975-7
50	Han DM , She WY , Zhang L . Association of the CD14 gene polymorphism C-159T with allergic rhinitis[J]. Am J Rhinol Allergy, 2010, 24(1): e1-e3. doi:10.2500/ajra. 2010.24.3411 . doi: 10.2500/ajra. 2010.24.3411
51	Leung TF , Tang NL , Sung YM , et al . The C-159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children[J]. Pediatr Allergy Immunol, 2003, 14(4): 255-260. doi: 10. 1034/j.1399-3038.2003.00048.x . doi: 10. 1034/j.1399-3038.2003.00048.x
52	Wang ZY , Sundy JS , Foss CM , et al . Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity[J]. J Asthma Allergy, 2013, 6: 81-92. doi:10.2147/JAA.S42695 . doi: 10.2147/JAA.S42695
53	Kabesch M , Hasemann K , Schickinger V , et al . A promoter polymorphism in the CD14 gene is associated with elevated levels of soluble CD14 but not with IgE or atopic diseases[J]. Allergy, 2004, 59(5): 520-525. doi:10. 1111/j.1398-9995.2004.00439.x . doi: 10. 1111/j.1398-9995.2004.00439.x
54	Kutsenko NL , Izmailova OV , Vesnina LE, et al . [Relationship of toll-like receptors 2 and 4 genes polymorphisms with allergic diseases with increased levels of specific IgE][J]. Tsitol Genet, 2012, 46(6): 59-66. PMID: 23285751.
55	Koppelman GH , Reijmerink NE , Colin Stine O , et al . Association of a promoter polymorphism of the CD14 gene and atopy[J]. Am J Respir Crit Care Med, 2001, 163(4): 965-969. doi:10.1164/ajrccm.163.4.2004164 . doi: 10.1164/ajrccm.163.4.2004164
56	Varadaradjalou S , Féger F , Thieblemont N , et al . Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells[J]. Eur J Immunol, 2003, 33(4): 899-906. doi:10.1002/eji.200323830 . doi: 10.1002/eji.200323830
57	de Guia RM , Echavez MD , Gaw EL , et al . Multifactor-dimensionality reduction reveals interaction of important gene variants involved in allergy[J]. Int J Immunogenet, 2015, 42(3): 182-189. doi:10.1111/iji.12200 . doi: 10.1111/iji.12200
58	Choi WA , Kang MJ , Kim YJ , et al . Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma[J]. J Asthma, 2012, 49(3): 243-252. doi:10.3109/02770903.2012.660294 . doi: 10.3109/02770903.2012.660294

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

Comments

Recommended 10

[1]	LIN Bin,WANGHui-ge . Functional endoscopic sinus surgery, FESS[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(6): 481 -487 .
[2]	. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 84 -87 .
[3]	. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(2): 116 -118 .
[4]	CHEN Wen-wen . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(5): 472 -472 .
[5]	ZHOU Bin,LI Bin . Endoscopic sinus surgery for 75 patients with chronic sinusitis and nasal polyps[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 24 -26 .
[6]	YANG Changliang,HUANG Zhiwu,YAO Hangqi,ZHU Yong,SNU Yi . Study on auditory brainstem response[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 9 -13 .
[7]	. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 89 -89 .
[8]	LUAN Jiangang,LIANG Chuanyu,WEN Yanjun,LI Jiong . Construction of RNAi expressing plasmid vector of pSIRENshuttle for EGFR gene silencing[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 4 -8 .
[9]	NIU Shanli,CHAI Maowen,LI Zhenxiu . Endoscopic rhinoplasty of inferior turbinate in 60 patients with chronic hypertrophic rhinitis[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 16 -18 .
[10]	. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 90 -91 .

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)

[1]	ZHANG Guiyang, HUANG He, XIAN Zhi, ZHANG Hanwen, XIE Guicai. Evaluation of clinical effects of sublingual immunotherapy with Dermatophagoides farinae drops in patients of different age groups with allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 60-65.
[2]	LIU Yan, WEI Ping, KOU Wei, HU Sijie, WU Xiaofang, LIU Mengya, CHEN Cheng, YAO Hongbing. Research of the relationship between adenoid hypertrophy and the common diseases of pediatric otolaryngology [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 149-154.
[3]	Junjun QIAN,Wencheng ZHOU,Zhongfei WU,Dongyun BU,Liqin WANG,Meiping LU,Lei CHENG. Analysis of sensitization to inhalant allergens in patients with allergic rhinitis from Jiangsu and Anhui areas [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 147-151.
[4]	Huiqin TIAN,Zhongfei WU,Ying LU,Lei CHENG. Association of vitamin D binding protein geneand CYP27B1 gene polymorphisms with mite-sensitized persistent allergic rhinitis among Han Chinese population [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 71-78.
[5]	Changyu QIU,Jun ZHOU,De′en ZHUANG,Qing YANG,Meiping LU,Lei CHENG. Artificial intelligence technology application in disclosing allergic rhinitis patients′ needs to otolaryngologists [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 88-94.
[6]	Meiping LU,Lei CHENG. Current status of genetic research on allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 36-41.
[7]	Yinshi GUO,Hui LU. Research progress of group Ⅱ innate lymphoid cells in the allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 9-12.
[8]	Qianhui QIU,Junxiao GAO. Synchronous control and long-term efficacy of specific immunotherapy for allergic rhinitis and asthma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 33-37.
[9]	QIN Ya′nan, WANG Lin, JIANG Yan, YAN Shu, CHEN Min, YU Longgang, LI Na. Characteristics of the distribution of inhaled allergens in patients with allergic rhinitis in Qingdao from 2008 to 2017 [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 67-72.
[10]	JIN Xing, HU Dayu, ZHU Li, DENG Furong, LIU Junxiu. Correlation between PM_2.5 and upper airway resistance in patients with allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 77-80.
[11]	LI Lisha, GUAN Kai, WANG Zixi, CUI Le. The effects of air pollutants on the severity of allergic rhinitis symptoms caused by cypress pollen [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 81-87.
[12]	HONG Haiyu, XU Guangfu, YANG Shuowei, SU Rongfei, HUANG Yili, CHI Mengshi,WANG Weihao,YANG Qintai. The prevalence and risk factors of bronchial asthma in patients with allergic rhinitis in Guangdong Province [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 94-98.
[13]	QI Yan, LIU Junqi, PENG Shuya, LUO Kai, ZHANG Mingxia, WANG Zhenlin. Therapeutic ecacy of endoscopic elective vidian neurectomy for moderate-severe persistent allergic rhinitis with chronic sinusitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 109-113.
[14]	CAO Cheng, XU Yu. Clinical compliance and related factors to sublingual immunotherapy in patients with allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 114-118.
[15]	HONG Dongdong, LIU Yuanxian, ZOU Lianqiang, WENG Juanling, DENG Wenxian. An analysis of 764 positive skin prick test results for Dermatophagoides farinae in patients with allergic rhinitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 119-123.

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

RichHTML

PDF (PC)

Abstract

Cite this article

share this article

Figures/Tables 6

References 58

Related Articles 15

Metrics

Comments

Recommended 10