Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE-mediated allergy

BACKGROUND: Immunoglobulin E (IgE)-mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations. METHODS: We investigated relationship among atopic phenotypes and two polymorphisms [C(-159)T and G(-1359)T] in the promoter of the CD14 gene in the Czech population. Polymerase chain reaction with restriction fragment length polymorphism analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n = 562) and random controls (n = 320). RESULTS: The CD14 allele or genotype distributions were similar in patients and control group. However, the frequency of the C allele of the C(-159)T polymorphism was higher in patients with positive skin prick tests for moulds than in patients without reactivity to this antigen (P < 0.002, Pcorr<0.01). In addition, we found that patients with homozygous genotype (GG) of the G(-1359)T polymorphism had marginally lower percentage of positive skin prick tests compared with the other genotypes (P < 0.029, Pcorr > 0.05). CONCLUSIONS: Our study supports the idea that CD14 gene variants may act as disease modifiers of IgE-mediated allergic diseases.     

CD14 polymorphisms,microbial exposure and allergic diseases: a systematic review of gene–environment interactions

Asthma and allergy may develop as a result of interactions between environmental factors and the genetic characteristics of an individual. This review aims to summarize the available evidence for, and potential effects of, an interaction between polymorphisms of the CD14 gene and exposure to microbes on the risk of asthma and allergic diseases. We searched PubMed, MEDLINE and Global Health databases, finding 12 articles which met inclusion criteria. Most studies reported a significant interaction between CD14 polymorphisms and microbial exposure. When stratified by age at microbial exposure (early life vs adult life), there was evidence of a protective effect of gene–environment interaction against atopy in children, but not adults. We also found different effects of interaction depending on the type of microbial exposures. There was no strong evidence for asthma and eczema. Future studies should consider a three‐way interaction between CD14 gene polymorphisms, microbial exposures and the age of exposure.     

Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency diseases. Cytokine production could be affected in CVID patients, whereas its alteration could be due to genetic polymorphisms within coding and promoter regions of the cytokine genes. This study was performed to analyse the proinflammatory cytokine single nucleotide polymorphisms in CVID. The allele and genotype frequencies of a number polymorphic genes coding tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α, IL‐1β, IL‐1R, IL‐1RA and IL‐6 were investigated and compared between two groups of CVID patients and controls. The IL‐6 GA genotype at position nt565 was significantly over‐represented in the patient group (P < 0·001), while the IL‐6 GG genotype at position ?174 (P = 0·006) and the GG genotype at position nt565 (P < 0·001) were significantly lower than controls. The TNF‐α AG genotype at position ?308 in the patient group was increased significantly in comparison with controls (P = 0·027), but the GG genotype at the same position was significantly decreased (P = 0·011). IL‐6 CA and GA haplotypes were the most frequent haplotypes in the patients (P < 0·005), whereas TNF‐α GA (P = 0·002) and IL‐6 GG (P < 0·001) haplotypes were decreased significantly in the patients in comparison with controls. Cytokine single nucleotide polymorphisms could have a role in pathophysiology of CVID. High production of TNF‐α is expected in some CVID patients based on the frequency of genotypes/haplotypes of these cytokine gene polymorphisms.     

Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations

We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI. The potential of these markers to enhance the efficiency of type 1 diabetes risk screening was then evaluated by analyzing them in Finnish and Swedish populations. Blood spots on filter paper were analyzed using PCR followed by sequence-specific hybridization and time-resolved fluorometry reading. Distribution of the genotypes at both positions differed significantly among the affected children compared to the controls. The risk genotypes (CC, AA) were significantly more common in Finland than in Sweden, both among patients and controls. The VNTR genotype homozygous for the protective class III alleles showed a significantly stronger protective effect than the heterozygote (p=0.02). Analyzing both SNPs enabled the detection of VNTR class III subclasses IIIA and IIIB. The observed significance between effects of the protective genotypes was due to the strong protective effect of the IIIA/IIIA genotype. IIIA/IIIA was the only genotype with significant discrepancy between protective effects compared to the other class III genotypes. These observations suggest that heterogeneity between the protective IDDM2 lineages could exist, and analyzing both -23HphI and -2221MspI would thus potentially enhance the sensitivity and specificity of type 1 diabetes risk estimation.     

高原世居藏族人群CD14基因单核苷酸多态性研究

目的 通过检测高原世居藏族人群CD14基因全长的序列信息,了解该地区藏族人群CD14基因单核苷酸多态性变化的遗传特点.方法 采用直接测序的方法检测40例西藏高原世居藏族人群CD14基因全长,将测序结果与美国国家生物技术信息中心(NCBI)及国际人类基因组单体型图计划(HapMap)数据库比对,确定高原藏族CD14基因SNP位点的位置、类型和频率,并与不同人群SNP等位基因频率进行分析比较.结果 高原世居藏族人群CD14基因总有效测序长度约为4259 bp,共发现9个CD14基因SNP位点,其中有6个位点在NCBI的dbSNP数据库中已经存在,新发现3个SNP位点分别为:SNP04 (2755 T＞G)、SNP07(3801 T＞C)、SNP08 (4192 T＞A).通过9个位点计算出4个主要单倍型,分别是CAGTCCTTG,频率为36.1％;CGGTCCTTG,频率为28.8％;CGGTCCTTC,频率为5.8％;CGATCCTTG,频率为3.8％.不同人群等位基因分析比较发现:在rs2563298位点,携带A等位基因在高原藏族人群的分布频率显著低于中国汉族(P=0.016)、欧洲(P =0.000)、日本(P =0.002)和非洲人群(P=0.001);在rs2569190位点,高原藏族人群携带G等位基因显著低于非洲人群(P =0.001),而与中国汉族(P=0.755)、日本(P =0.635)和欧洲人群(P=0.467)分布相似,差异无统计学意义.在rs2569192位点,C等位基因在高原藏族人群低于欧洲人群(P =0.035),而与中国汉族(P =0.837)、日本(P =0.266)和非洲人群(P=0.064)分布相似差异无统计学意义.结论 高原世居藏族人群CD14基因SNPs分布具有自身的遗传特征,本项研究将为进一步探讨高原地区藏族人群CD14基因相关疾病发病机制提供科学依据.     

Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE-mediated allergy

IgE-mediated allergy is a common chronic disorder resulting from interactions between genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a region linked to asthma and bronchial hyperresponsiveness. We investigated the relationship among atopic phenotypes and six polymorphisms in the CD14 gene. Polymerase chain reaction with RFLP analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n=282) and random controls (n=187). No significant differences in allele or genotype frequencies for individual polymorphisms between patients and controls were found. However, when atopic patients were subdivided into subjects with positive and with negative skin prick tests for separate antigens, T allele of the 1341G/T polymorphism was significantly associated with positive reactivity to mites (P=0.007) and moulds (P=0.041). Similarly, the C allele frequency of the −159C/T variant was increased in patients with positive skin prick tests for mites (P=0.046) and moulds (P=0.056). In haplotype analysis, the common −1619A/−1359G/−550C/−159C/+1188G/+1341T haplotype was associated with positive reaction to these antigens (P values: 0.0008–0.0035). Our study supports the idea that CD14 plays a role in IgE-mediated allergic diseases, and its gene polymorphisms can be important for manifestation of these disorders.     

β2肾上腺素受体基因Arg16Gly位点多态性与华南人群哮喘相关性研究

目的探讨β2肾上腺素受体基因(ADRB2)SNP位点rs1042713即突变位点Arg16Gly的多态性与华南汉族人群支气管哮喘发病的相关性。方法采用病例对照研究,利用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)对rs1042713进行基因分型,对实验结果运用χ2检验和二分类Logistic回归进行统计学相关性分析。结果 rs1042713多态位点AA、AG、GG 3种基因型在哮喘患者的频率为18.7%、76.0%和5.3%,与对照组(33.8%,44.6%和21.6%)相比具有显著差异(χ2=36.28,P<0.001);对年龄和性别进行校正后,发现相对于AA+GG基因型,携带AG基因型的哮喘发病风险增加(OR=4.37,95%CI:2.64~7.23)。结论华南汉族人群哮喘的发病机制可能与SNP rs1042713位点的单核苷酸多态性有关,杂合子基因型AG为其发病的危险因素。     

MMP14基因单核苷酸多态性在广西百色地区壮族人群中的分布

目的研究膜型基质金属蛋白酶-1(membrane-type 1 matrix metalloproteinase,MT1-MMP或MMP14)基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)各等位基因及基因型在广西百色地区壮族人群中的分布频率。方法采用Multiplex SNaPshot SNP分型技术对百色地区624例壮族个体的MMP14染色体基因组的3个SNP进行基因分型。结合HapMap4个人群(HapMap-CEU、HapMap-YRI、HapMap-JPT和HapMap-HCB)的SNPs分型数据,分析这5个人群的遗传结构。结果壮族人群MMP14的基因型分布频率为:rs2269213(CC 55.4%、CA 39.2%和AA 5.4%)、rs2236303(CC 25.2%、CT50.8%和TT 24.0%)和rs743257(CC 37.0%、CT 48.7%和TT 14.3%)。MMP14基因SNPs在壮族人群的分布频率与HapMap-CEU、HapMap-YRI和HapMap-JPT的差异有统计学意义(P<0.05)。结论广西百色地区壮族人群中存在MMP14基因多态性,且与HapMap-CEU、HapMap-YRI和HapMap-JPT有差异的遗传成分存在,这种差异对人类学研究可能起重要的作用。     

腰椎间盘退变与COL9A2基因单核苷酸多态性的相关性

背景：有研究证实,腰椎间盘退变与基因有密切关系。 目的：探讨COL9A2基因单核苷酸多态性(rsl2722877、rs3737820和rs209914)与腰椎间盘退变性疾病的关系。 方法：腰椎间盘退变性疾病患者280例,年龄、性别匹配的268例非腰椎间盘退变性疾病患者作为正常对照组,均来自广西壮族。收集腰椎间盘退变性疾病患者、非腰椎间盘退变性疾病患者的血液样本,提取基因组DNA,设计针对COL9A2基因rsl2722877、rs3737820和rs209914位点的PCR引物、TaqMan探针,利用TaqMan探针技术对rsl2722877、rs3737820和rs209914位点进行PCR荧光分型。采用SPSS17.0软件进行等位基因频率及基因型频率分析。 结果与结论：rsl2722877、rs3737820和rs209914位点的各基因型与等位基因频率分布在病例组和对照组之间均差异有显著性意义(P < 0.05)。COL9A2基因单核苷酸多态性rsl2722877、rs3737820和rs209914与广西壮族人群腰椎间盘退变性疾病易感性密切相关。     

Constitutive nitric oxide synthase gene polymorphisms and house dust mite respiratory allergy in an Algerian patient group

Genetic polymorphisms in neuronal nitric oxide synthase (NOS1) and calmodulin-dependent endothelial NOS (NOS3) genes are known to influence the course of allergic respiratory disorders. We investigated the role of NOS1 -84 G-->A and NOS3 -786 T-->C, 894 G-->T and 27 base pair (bp) repeat polymorphisms in 125 patients suffering from asthma and/or rhinitis and monosensitized against Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. We found a higher frequency of the -786 C NOS3 allele in patients than in controls [corrected P value (Pc) = 0.04], especially in female cases (Pc = 0.02) and that the 'ab' genotype of the 27-bp polymorphism was significantly associated with specific immunoglobulin E production against Dpter (P = 0.006). This study brings further support for the participation of NOS3 gene polymorphism in the pathogenesis of respiratory allergic disorders.     

Association of single nucleotide polymorphisms in the IL-18 gene with sarcoidosis in a Japanese population

Interleukin-18 (IL-18) and interleukin-12 (IL-12) synergistically stimulate interferon-gamma (IFN-gamma) production from Th1 cells. The levels of serum IL-18 and IFN-gamma and bronchoalveolar lavage fluid IL-18 were elevated in patients with sarcoidosis. The polymorphisms of the IL-18 gene may play a possible role in expression regulation of the gene. We investigated the roles of the polymorphisms in the development of sarcoidosis. We examined two single nucleotide polymorphisms of the IL-18 gene in 119 patients with sarcoidosis and 130 healthy control subjects. Our results showed that the frequency of sarcoidosis patients with the CA genotype at position -607 was significantly higher than that with the AA genotype (OR = 2.200) and a significantly higher proportion of patients had the C allele at -607 compared with that of the controls (OR = 2.123). No significant differences were seen in the distribution of the genotypes or phenotype frequencies at position -137. There was no specific organ involvement associated with a certain genotype or phenotype. In IL-18 gene polymorphisms, the C allele at position -607 might be a genetic risk factor for sarcoidosis in this Japanese population.     

Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children

Many studies have shown the implication of CD14 and toll-like receptors (TLRs) 2, 4 and 9 in the pathogenesis of asthma or atopy. To evaluate the association of CD14 and TLRs gene polymorphisms with asthma or atopy, 210 asthmatic children, 224 controls and 80 families were enrolled in this study. Six single nucleotide polymorphisms TLR2 (+2408 G-->A), TLR4 (+1196 C-->T), TLR4 (+896 A-->G), TLR9 (-1237 T-->C), TLR9 (-1486 T-->C) and CD14 (-159 C-->T) were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism in the case-control and family study. The -1237C allele in TLR9 gene polymorphisms was associated with increased risk of asthma [odds ratio 1.53, 95% confidence interval (1.03-2.27)], although no statistically significant differences in allele or genotype frequencies of four other TLRs polymorphisms were evident between the asthmatic and control groups. The CD14 -159 C allele was found to be significantly higher in the asthmatic group when compared with controls (P=0.0006<0.05). Transmission disequilibrium test of 80 asthmatic families showed significant transmission of the -159 C allele in the CD14 gene to asthma-affected offspring. It was concluded that TLR9 and CD14 gene polymorphisms may contribute to an inherited predisposition to asthma in Tunisian children.     

Toll样受体9基因启动子单核苷酸多态性与儿童变应性哮喘的相关性

目的 研究Toll样受体9(toll-like receptor 9,TLR9)基因启动子区单核苷酸多态性在浙江汉族儿童中的分布,探讨其与哮喘易感性及其表型之间的相关性.方法 对312例变应性哮喘患儿(哮喘组)和339名健康儿童(对照组)采用DNA直接测序法检测TLR9基因-1486(rs187084)和-1237(rs5743836)单核苷酸多态性;采用ELISA法检测两组不同基因型血清干扰素γ(interferon-γ,IFN-γ)、白细胞介素12(interleukin-12,IL-12)和白细胞介素4(interleukin-4,IL-4)水平;采用化学发光法检测血清总免疫球蛋白E(immunoglobulin E,IgE)水平;采用酶免疫荧光法检测血清变应原特异IgE.结果 (1)哮喘组和对照组均存在-1486位点T→C突变,哮喘组TT、TC和CC 3种基因型的频率分别是3 8.8%、48.4%和12.8%,对照组分别是41.0%、44.3%和14.7%;未发现-1237位点存在多态性.(2)哮喘组和对照组-1486位点各基因型的频率分布差异无统计学意义(P＞0.05),年龄分层后比较差异也无统计学意义(P＞0.05).(3)哮喘组-1486位点3种基因型的血清IFN-γ和IL-4水平差异有统计学意义(P＜0.01),CC基因型的IFN-γ水平较低而IL-4水平较高;对照组2种细胞因子的差异无统计学意义(P＞0.05).哮喘组和对照组血清IL-12水平在3种基因型间差异均无统计学意义(P＞0.05).(4)哮喘组-1486位点不同基因型血清总IgE水平差异无统计学意义(P＞0.05).结论 浙江汉族儿童不存在TLR9基因-1237位点多态性.TLR9基因-1486 C/T位点单核苷酸多态性与浙江汉族儿童哮喘易感性、血清IL-12及总IgE水平无关;-1486 C/T位点多态性与哮喘患儿血清IFN-γ和IL-4水平有关联,CC基因型的IFN-γ水平较低而IL-4水平较高.

Abstract：

Objective To investigate the distribution characteristics of the single nucleotide polymorphisms (SNPs) in the promoter region of the toll-like receptor 9 gene (TLR9)in Chinese Han children from Zhejiang province, and their associations with asthma susceptibility and phenotypes. Methods A case-control study was conducted. A total of 312 asthmatic children aged between 1.9 and 11.6 and 339 age matched healthy controls were enrolled in this study from April 2007 to November 2008. The -1486 C/T in rs187084 and -1237 C/T in rs5743836 loci of the TLR9 gene were genotyped by direct DNA sequencing of the PCR products. Serum levels of IFN-γ, IL-12 and IL-4 were detected by enzyme linked immunosorbent assay. Serum levels of total IgE were detected by chemiluminescence, and serum levels of ildren (P＜0.01). The CC genotype had the lowest levels of serum IFN-γand the highest levels of serum IL-4 among the three genotypes. There were no significant differences in these cytokines among the healthy controls (P＞0.05). No statistical differences of serum IL-12 were found among the three genotypes in the two groups (P＞0.05). (4) There were no significant differences of total IgE (log-transformed) among the three genotypes in the asthmatic children (P＞0. 05). Conclusion The -1237 C/T polymorphism of TLR9 gene was not detected in Chinese Han children in this study. The - 1486 C/T polymorphism was associated with the levels of serum IFN-γ and IL-4 in children with asthma.However, there were no correlations between the -1486C/T polymorphism and serum IL-12 levels, total IgE levels or asthmatic susceptibility.     

No association between a common single nucleotide polymorphism,rs4141463, in the MACROD2 gene and autism spectrum disorder

The Autism Genome Project (AGP) Consortium recently reported genome‐wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case–control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non‐centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case–control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta‐analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944–1.133), with a P‐value of 0.5 for ASD and OR of 0.99 (95% CI 0.88–1.11) with P‐value = 0.85 for the Autism (A) sub‐group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. © 2011 Wiley‐Liss, Inc.     

The effect of polymorphisms at the CD14 promoter and the TLR4 gene on asthma phenotypes in Turkish children with asthma

BACKGROUND: Endotoxin, with its potential to enhance type 1 immunity, is a significant player in the hygiene hypothesis. The combined effects of the genetic variants of various molecules in the endotoxin response pathway on asthma related phenotypes are largely unknown. OBJECTIVE: To investigate the effects of the genetic variants of CD14 and TLR4 genes on asthma phenotypes in a large number of asthmatic children. METHODS: 613 asthmatic children were genotyped at the CD14-C159T, TLR4-A896G and TLR4-C1196T loci. IgE, eosinophil numbers and FEV1 were compared in 327 children who were not on any controller medications and were symptom free. Multivariate logistic regression was used to determine the factors associated with total IgE. RESULTS: Among children with atopic asthma, total IgE levels were significantly different among the three genotypes in the co-dominant model [CC: 435 kU/l (interquartile range: 146-820); CT: 361 (140-710); TT 204 (98-435), P = 0.035]. TT genotype was significantly and independently associated with lower IgE levels (OR: 0.5 95%; CI = 0.28-0.90, P = 0.021). Both TLR4-A896G and TLR4-C1196T polymorphisms were more frequent in the mild asthma group with atopy (P = 0.032, 0.018, respectively). The combined effects of the genetic variants in CD14 and TLR4 genes did not improve the observed associations. CONCLUSION: Our study demonstrates that the CD14-C159T promoter variant influences total IgE levels and also indicates that the T allele has a more profound effect on total IgE in children with atopic asthma. Polymorphisms in the TLR4 gene may be associated with milder forms of disease in atopic asthmatics in the population studied.     

VDR基因多态性、环境因素与重庆地区肺结核病的联系及交互作用研究

目的探讨维生素D受体(VDR)基因多态性、环境因素与结核病发病的相关性,以及因素间的交互作用。方法采用病例对照研究方法,选择198例确诊肺结核病例为病例组,按年龄、性别成组匹配195例健康人为对照组。采用高分辨率溶解曲线技术(HRM)检测VDR基因TaqⅠ、FokⅠ多态性位点的基因型,同时收集研究对象环境因素暴露情况,以单因素和多因素非条件Logistic回归分析的方法,分析VDR基因多态性、环境因素与结核病的联系及其交互作用。结果结核病患者接触史、吸烟、人均居住面积小于10 m2、居室通风不良、工作强度大以及VDR基因FokⅠ-ff基因型与结核病易感性相关(P<0.05),VDR基因FokⅠ-ff基因型、吸烟及结核病患者接触史在结核病发生中存在明显的交互作用(P<0.05)。结论 VDR基因多态性、环境因素与结核病的发病有关,且存在一定的交互作用。     

HTRA1基因单核苷酸多态性与类风湿性关节炎的关联性研究

目的 探讨HTRA1基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)和类风湿性关节炎(rheumatoid arthritis,RA)及其患者血清类风湿因子(rheumatoid factor,RF)、C反应蛋白((C-reactive protein, CRP)之间的相关性.方法 采用Snapshot法测定344例RA患者和288名正常健康人HTRA1基因5个SNPs(rs2014307、rs2248799、rs2300433、rs714816、rs2268356)位点基因型,终点散射比浊法测定RA患者血清RF和CRP水平.结果 RA组HTRA1基因SNPs(rs2014307、rs2248799、rs2300433、rs714816、rs2268356)基因型与正常对照组间差异均无统计学意义(P>0.05),单倍型分析也显示H豫A1基因RA组与正常对照组间差异无统计学意义(P>0.05),RA患者HTRA1基闪SNPs位点(rs2014307、rs2248799、rs714816、rs2268356)不同基因型之间血清RF水平比较差异无统计学意义(P>0.05),而rs2300433位点基因型(AA+AG)组的RF水平明显高于GG组((P<0.05).结论 已分析的与HTRA1基因相关的5个SNPs与中国汉族人种RA遗传易感性不相关,HTRA1基因rs2300433位点不同基因型RA患者体内RF水平有差别,HTRA1基因表达的丝氨酸蛋白酶可能参与了RA患者RF的表达.     

湖北汉族变应性哮喘患者GPR154基因单倍型分析

目的探讨G蛋白偶联受体154(Gprotein-coupled receptor154,GPR154)基因多态性与湖北汉族变应性哮喘易感性间的关系。方法用聚合酶链反应和限制性片段长度多态性对145例变应性哮喘患者和120名健康人群GPR154基因的SNP563704和SNP522363位点的多态性进行分析。结果(1)变应性哮喘患者SNP563704 CC、CT和TT基因型频率是0.324、0.524和0.152;与对照组相比差异无统计学意义(χ2=1·880,P>0.05);变应性哮喘组不同基因型间血清总IgE水平差异无统计学意义(F=0.714,P>0.05)。(2)变应性哮喘患者SNP522363CC、CG和GG基因型频率是0.289、0.521和0.190;与对照组相比差异无统计学意义(χ2=0.700,P>0.05);变应性哮喘组不同基因型间血清总IgE水平差异无统计学意义(F=0·083,P>0.05)。(3)对SNP522363和SNP563704进行单倍型分析,4种频率大于0.03的单倍型在哮喘组和对照组间差异有统计学意义(χ2=16.50,P<0.01)。哮喘组CT和GT单倍型频率显著高于对照组,差异有统计学意义(P=0.015;P=0.002)。结论湖北汉族变应性哮喘易感性与单个的单核甘酸多态性无关,但与SNP522363和SNP563704组成的单倍型显著相关。