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

摘要/Abstract

摘要： 目的

Toll样受体（TLR）信号通路一直是变应性鼻炎（AR）和哮喘等变态反应性疾病的研究热点，研究TLR通路基因单核苷酸多态性（SNPs）与AR发病的相关性及机制。

方法

采用基于医院的病例-对照研究，选择持续性AR患者452例及正常人群495例。通过生物信息学数据库系统筛选TLR通路基因6个SNPs，分别是TLR2的rs7656411、rs76112010、rs7682814，CD14的rs2563298、rs2569190、rs2569191。采用TaqMan技术对SNPs进行分型，ImmunoCAP100变应原体外检测系统测定血清总IgE、特异性IgE，分析SNPs与AR发病率的相关性，并探讨基因-基因相互作用。

结果

CD14的rs2563298、rs2569191基因分布在AR组与对照组比较有统计学意义（P<0.05）。TLR2的rs7656411和CD14的rs2563298、rs2569191在AR伴随哮喘组与正常对照组中基因分布有明显差异。此外TLR2的rs7656411在AR男性组和有家族史组与对照组的基因分布有明显差异，CD14的rs2563298、rs2569191在AR分组中与对照组均有明显差异。基因交互发现rs7656411，rs2563298、rs2569191三个位点存在阳性关联。

结论

TLR通路基因TLR2、CD14多态性与AR发病风险及其临床表型存在一定相关性。

关键词: 变应性鼻炎, Toll样受体, CD14, 单核苷酸多态性, 遗传学关联研究

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

中图分类号:

R765.21

陈若希,张清照,陆美萍,朱歆洁,程雷. TLR通路基因多态性与变应性鼻炎的关联研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 79-87.

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.

图/表 6

表1

表2

病例组和对照组研究对象的临床特征"

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）

表2

表3

TLR2和CD14多态性基因分型及在病例与对照组中的频率分布"

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

表3

表4

表5

图1

参考文献 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

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed

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]	张贵阳,黄河,冼志,张汉文,谢桂彩. 粉尘螨滴剂舌下含服免疫治疗对不同年龄段变应性鼻炎患者的临床效果评估[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 60-65.
[2]	刘燕,魏萍,寇巍,胡思洁,武小芳,刘萌雅,陈成,姚红兵. 儿童腺样体肥大与耳鼻咽喉科常见疾病关系的研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 149-154.
[3]	钱俊俊,周文成,吴中飞,卜冬云,汪李琴,陆美萍,程雷. 苏皖地区变应性鼻炎患者吸入性变应原谱分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 147-151.
[4]	田慧琴,吴中飞,陆莹,程雷. GC和*CYP27B1*基因多态性与汉族人群尘螨致敏的持续性变应性鼻炎的关联研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 71-78.
[5]	陆美萍,程雷. 变应性鼻炎的遗传学研究现状[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 36-41.
[6]	郭胤仕,卢慧. Ⅱ型固有淋巴细胞在变应性鼻炎发病机制中的作用[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 9-12.
[7]	邱前辉,高俊潇. 特异性免疫治疗对过敏性鼻炎和哮喘的同步控制和远期疗效[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 33-37.
[8]	秦雅楠,王琳,姜彦,闫舒,陈敏,于龙刚,李娜. 2008~2017年青岛地区变应性鼻炎常见吸入性变应原分布[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 67-72.
[9]	金兴,胡大宇,朱丽,邓芙蓉,刘俊秀. PM_2.5与变应性鼻炎患者上气道阻力的相关性研究[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 77-80.
[10]	李丽莎,关凯,王子熹,崔乐. 大气污染物对于变应性鼻炎症状严重度的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 81-87.
[11]	洪海裕, 许光福, 杨烁伟,苏荣飞,黄伊厘,池梦诗,王玮豪,杨钦泰. 探究广东地区变应性鼻炎合并支气管哮喘的危险因素[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 94-98.
[12]	齐岩,刘俊其,彭舒娅,罗凯,张名霞,王振霖. 鼻内镜下选择性翼管神经切断术对伴有变应性鼻炎的慢性鼻窦炎的疗效观察[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 109-113.
[13]	曹成,许昱. 变应性鼻炎患者舌下免疫治疗的临床依从性192例分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 114-118.
[14]	洪冬冬,刘元献,邹练强,翁镌凌,邓文娴. 变应性鼻炎患者粉尘螨皮肤点刺试验阳性764例结果分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 119-123.
[15]	杜经纬,冯俊,马鹏,李志勇,李红光. 鼻腔冲洗联合鼻用糖皮质激素对AR患者FeNO、肺功能及生活质量的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 124-127.