Allergic diseases mentioned in this review is regarding to I type allergic inflammation induced by an IgE-mediated reaction, including asthma, allergic rhinitis, atopic dermatitis and food allergy. It is convinced that allergic diseases belong to multiple genes diseases and are controlled by both genetic and environmental factors. Meanwhile there exists gene-gene as well as gene-environment interactions during the development of the disease. The aim of this review is to summarize the toolkit, advance, inherent difficulties and future clinical application prospect in genetic studies of allergic disease.
Asthma ; genetics ; Gene-Environment Interaction ; Humans ; Hypersensitivity ; genetics ; Immunoglobulin E ; Rhinitis, Allergic, Perennial ; genetics ; Rhinitis, Allergic, Seasonal ; genetics ; Risk Factors

OBJECTIVETo explore the effects of genetic factors on the occurrence of allergic rhinitis (AR).

METHODSThe morbidity rate of AR was surveyed by multistage sampling among 95 300 individuals (23,825 families) in Natong region, Jiangsu province. And a genetic epidemiologic investigation on AR was carried out to estimate the segregation ratio and heritability (h2) of AR by the methods of Li-Mantel-Gart and Falconer respectively.

RESULTSThe morbidity rate of AR in Natong region was 1.20% (Male 1.21%, Female 1.18%, no statistical significance between them); By the data of the AR ancestry, the segregation ratio of AR in Nantong region was 0.078, significantly less than 0.25, and the genetic model belonged to polygenetics. The 1st, the 2nd, and the 3rd generation h2 of AR were (82.6 +/- 2.19)%, (80.8 +/- 2.93)%, (78.4 +/- 7.04)%. The h2 of AR was (81.86 +/- 1.70)%. In the ancestry of AR, the morbidity rate of the 1st generation with AR was 12.11%; the 2nd generation with AR was 5.12%; the 3rd generation with AR was 2.75%; and the morbidity rate of AR in general population was 1.20%.

CONCLUSIONSThe heredity in family with AR is obvious. Several genes plus the environmental factors may cause AR, which accords with the characteristics of the polygene heredity disease.

China ; epidemiology ; Female ; Humans ; Male ; Multifactorial Inheritance ; Prevalence ; Rhinitis, Allergic, Perennial ; epidemiology ; genetics ; Rhinitis, Allergic, Seasonal ; epidemiology ; genetics

The relationship of interleukin-4 (IL-4) C-33T and C-590T (C-589T) gene polymorphisms with allergic rhinitis was analyzed. Data about the case control studies of IL-4 gene promoter polymorphisms [C-33T and C-590T (C-589T)] and their association with allergic diseases and correlation between serum IL-4 levels and allergic rhinitis were retrieved. The Stata 12.0 statistical software was applied to analyze the correlation between IL-4 gene polymorphisms and allergic rhinitis. The meta-analysis result of TT/CC genotype of -590 (-589) polymorphism showed a significant association with allergic diseases [OR=1.93, 95% CI (1.61-2.31), P=0.00]. Meta-analysis of the TT+TC versus CC genotype of IL-4 C-33/T polymorphism revealed significant associations with allergic diseases [OR=3.23, 95% CI (1.13-9.25), P=0.03]. Meanwhile, there was a significant correlation between serum IL-4 levels and allergic rhinitis [OR=2.52, 95% CI=(1.80-3.23), P=0.00]. IL-4 gene -590 TT genotype may increase the risk of allergic rhinitis and the T allele mutation of -33 might be correlated with allergic rhinitis.
Gene Frequency ; Genotype ; Humans ; Interleukin-4 ; blood ; genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; genetics ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; blood ; genetics ; Risk Factors

OBJECTIVE: To investigate the differences of IL-4, IFN-gamma gene promoter methylation of allergic rhinitis patients between Uygur and Han people of Xinjiang. METHOD: Methylation-specific PCR (MSP) detected IL-4, IFN-gamma gene methylation of each of 50 patients with allergic rhinitis in Uygur and Han. RESULT: Complete IL-4 gene promoter methylation rate was 44% (22/50) and 48% (24/50) in Uygur and Han AR patients, un-methylation was 26% (13/50) and 22% (11/50), coexistence rate of methylation and un-methylation was 30% (15/50) and 30% (15/50). Complete IFN-gamma gene promoter methylation rate was 12% (6/50) and 16% (8/50) in Uygur and Han AR patients, un-methylation was 8% (4/50) and 10% (5/50), coexistence rate of methylation and unmethylated was 80% (40/50) and 74% (37/50). Distribution of IL-4 gene methylation between Han and Uygur AR patients had no statistically significant (P > 0.05). Distribution of IFN-gamma gene methylation between Han and Uygur AR patients had no statistically significant (P > 0.05). CONCLUSION There is no difference of IL-4, IFN-gamma gene methylation in patients between the Han and Uygur.
Adult ; China ; epidemiology ; DNA Methylation ; Epigenesis, Genetic ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Humans ; Interferon-gamma ; genetics ; Interleukin-4 ; genetics ; Male ; Promoter Regions, Genetic ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; epidemiology ; genetics

OBJECTIVE: To evaluate the role of brain-derived neurotrophic factor (BDNF) in allergic rhinitis of rat. METHOD: Thirty SD rats free of disease were randomly divided into two groups. A model of allergic rhinitis rat was established by using ovalbumin intraperitoneal immunization and intranasal antigen challenge. The nasal mucosa from 18 out of 20 AR models as well as 10 normal controls were studied for expression of BDNF mRNA by reverse transcription-polymerase chain reaction (RT-PCR). RESULT: BDNF/beta-actin ratio in AR models was significantly higher than control (0.49+/-0.07 vs 0.28+/-0.01, P<0.05). CONCLUSION BDNF played an important role in the development of allergic rhinitis of rat.
Animals ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Disease Models, Animal ; Nasal Mucosa ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic, Perennial ; metabolism

OBJECTIVETo investigate whether the local application of IL-12 gene with EBV-plasmid vector to nasal mucosa could prevent allergic inflammation in murine allergic rhinitis model.

METHODSThirty-six BALB/C mice were randomly divided into allergic rhinitis group gene therapy group and control group. In mice with OVA-induced allergic rhinitis, the EBV/lipoplex (a novel cationic lipid combined with EBV-plasmid vector, pGEG. mIL-12) was locally administered into nasal mucosa before OVA challenge. The expression of IL-12 mRNA and protein, the change of eosinophilia and mast cell, and Th2 cytokine production in the nasal mucosa were measured.

RESULTSThe amounts of IL-12 mRNA positive cells and IL-12 positive cells in nasal mucosa of gene therapy group were significantly higher than that of allergic rhinitis group (P < 0.01 and P < 0.05). The amount of eosinophils, mast cells, and the level of IL-5 expression in nasal mucosa in allergic rhinitis group were significantly higher than those in gene therapy group and control group (P < 0.01). The level of total IgE of peripheral blood in allergic rhinitis group was significantly higher than that in gene therapy group and control group (F = 1216.21, P < 0.01).

CONCLUSIONSThese findings indicated that IL-12 mRNA and protein were expressed effectively after the local administration of pGEG. mIL-12 in the nasal mucosa. The local application of pGEG. mIL-12 is effective in modulating nasal allergic response and may be a convenient method for future approach to allergic rhinitis.

Animals ; Genetic Therapy ; Genetic Vectors ; Interleukin-12 ; genetics ; therapeutic use ; Male ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Perennial ; therapy

OBJECTIVETo investigate the level of mRNA expression of complement C3 and C4 in rat nasal mucosa and to reveal the relationship with the pathogenesis of allergic rhinitis (AR) .

METHODSTwenty healthy SD rats were randomly divided into AR group and control group, 10 rats for each group. Ten rats was sensitized and intranasally challenged by ovalbumin and Al (OH)3 (as supplement) as allergic rhinitis models, and the control group was treated by saline. RT-PCR was performed to investigate the level of mRNA expression of complement C3 and C4 in nasal mucosa of both groups.

RESULTSC3 and C4 mRNA were detected in both groups. The relative intensity of gene expression was measured. The relative intensity of C3 mRNA expression was 6183+/-1376 in AR group, 4444+/-989 in control group, C4 mRNA was 4398 +/-948 in AR group, and 2771+/-407 in control group. Expression of C3 and C4 in AR group was higher than that of the controls ( P < 0. 05) .

CONCLUSIONThe high level of C3 and C4 mRNA expression in nasal mucosa of rats with allergic rhinitis suggests that C3 and C4 are involved in the immunopathology of allergic rhinitis. The result implies that complement system involved in the rat's allergic rhinitis is possibly activated through the classical pathway.

Animals ; Complement C3 ; metabolism ; Complement C4 ; metabolism ; Female ; Male ; Nasal Mucosa ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic, Perennial ; metabolism

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.
Asthma/genetics ; Exons/genetics ; Gene Frequency/genetics ; Humans ; Membrane Proteins/*genetics/metabolism ; Polymorphism, Single Nucleotide/*genetics ; Promoter Regions (Genetics)/genetics ; Research Support, Non-U.S. Gov't ; Respiratory Hypersensitivity/*genetics ; Rhinitis, Allergic, Perennial/genetics ; Th1 Cells/metabolism

IL-28RA is one of the important candidate genes for complex trait of genetic diseases, but there is no published information of the genetic variation in this gene. We scanned the seven exons and their boundary introns sequence of IL-28RA including the promoter regions to analyze genetic variation sites, and identified eighteen single nucleotide polymorphisms (SNPs) and two variation sites. We chose seven SNPs (g.-1193 A>C, g.-30 C>T, g.17654 C>T, g.27798 A>G, g.31265 C>T, g.31911 C>T and g.32349 G>A) of them for large sample size genotyping, and assessed the association of genotype and allele frequencies of these SNPs between allergic rhinitis patients and non-allergic rhinitis controls. We also compared the genotype frequencies between Korean controls and Han Chinese control or Korean Chinese control. We investigated the frequencies of haplotype constructed by these SNPs between allergic rhinitis patients and non-allergic rhinitis controls. Our results suggested that the g.32349 G>A polymorphism of IL-28RA might be associated with susceptibility to allergic rhinitis (P=0.032), but seems to have no relationship with serum total IgE levels. The haplotype frequencies by these SNPs also show significant association between controls and allergic rhinitis patients.
Variation (Genetics) ; Rhinitis, Allergic, Seasonal/blood/*genetics ; Rhinitis, Allergic, Perennial/blood/*genetics ; Receptors, Cytokine/*genetics ; Promoter Regions (Genetics)/genetics ; Polymorphism, Single Nucleotide/*genetics ; Male ; Immunoglobulin E/blood ; Humans ; Haplotypes ; Genotype ; Genetic Predisposition to Disease/genetics ; Gene Frequency ; Female ; Exons/genetics ; Case-Control Studies ; Alleles ; Adult

OBJECTIVETo investigate the distribution characteristics of the single nucleotide polymorphisms (SNPs) of the human CD14 gene in Chinese Han ethnic group children in Wenzhou, and their association with atopic diseases.

METHODSTotally 113 cases were recruited in atopic disease group who met the following criteria: 2 - 12 years old, clinically diagnosed as asthma or allergic rhinitis or atopic dermatitis, elevation of serum total IgE levels and serum specific IgE. Sixty-seven healthy children were enrolled in control group. The related regions of CD14 gene were sequenced to identify and characterize the SNPs, and plasma TIgE and SIgE were detected by immunoassay system and uniCAP system, respectively. The frequency of genotypes and alleles between two groups, as well as the levels of IgE in different genotypes, were compared.

RESULTSCD14/-159 SNP was present in Han ethnic group population of Wenzhou. The frequency of each genotype was 57.0% (TT), 28.0% (TC), 15.0% (CC) in normal children, and 46.9% (TT), 35.4% (TC), 17.7% (CC) in atopic children. No significant difference was found in the distribution of CD14/-159 polymorphism between atopic children and healthy control (chi(2) = 1.918, P > 0.05) according to Hardy-Weinberg principle statistics. There were no significant difference in frequency of each genotype between boys and girls. No significant difference was found in the total plasma IgE levels among groups of TT genotypes [(2520 +/- 460) IU/L], TC genotypes [(2400 +/- 460) IU/L] and CC genotype [(2500 +/- 460) IU/L] (F = 0.807, P > 0.05).

CONCLUSIONCD14/-159 SNP is present in Han ethnic group children in Wenzhou, and other SNP in CD14 gene was not found. TT genotype was the primary genotype in CD14/-159 SNP in the children studied. No relationship between CD14/-159 SNP and atopic disease or serum total IgE level was found.

Asian Continental Ancestry Group ; genetics ; Asthma ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; Dermatitis, Atopic ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Immunoglobulin E ; blood ; Lipopolysaccharide Receptors ; genetics ; Male ; Polymorphism, Single Nucleotide ; Rhinitis, Allergic, Perennial ; genetics