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Background & objectives: ADAM33 is implicated as a potentially strong candidate gene for asthma and bronchial hyper-responsiveness. Many polymorphisms of ADAM33 have been studied along with ADAM33 expression in various cells of the lungs. Haplotype analysis also showed association with asthma in different populations across the world. Therefore, the aim of this study was to perform a comprehensive screening of ADAM33 polymorphisms in adult patients with asthma. Methods: Thirty five polymorphisms of ADAM33 were genotyped in 55 patients with asthma and 53 controls. The association of single nucleotide polymorphisms (SNPs) and haplotypes with phenotypes of asthma was analysed. Results: The genotype, minor allele frequency, odds ratio and Hardy–Weinberg equilibrium did not show any significant difference among cases and controls. No association was found between SNPs of ADAM33 with the severity of asthma. Correlation analysis of ADAM33 SNPs to the phenotypes, based on clinical variables and allergen sensitization, did not show significant difference. Haplotype analysis showed that rs2280090 and rs2280091 were associated with asthma in the patient group. Interpretation & conclusions: Haplotype analysis showed an association of the two SNP variations with asthma. These SNPs lead to amino acid change and are prone to phosphorylation, which may affect expression levels and protein function of ADAM33 and asthma susceptibility.
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Bronchial asthma is one of the most common diseases in children's respiratory system.Its frequent attacks seriously affect children's health,learning and life,bring great economic burden and mental pressure to families,leading to huge medical and health resources consuming.Many scholars have studied that ADAM33 is a susceptible gene for asthma.This article reviews the relationship between ADAM33 gene polymorphism and asthma,the pathogenesis of ADAM33 in asthma and the new progress in the treatment of ADAM33.
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Objective To explore the association between Q-1 and T1 locus polymorphism in ADAM33 gene and chronic obstructive pulmonary disease in Han population in northern Guizhou by detecting Q-1 and T1 locus polymorphism in ADAM33 gene in patients with COPD in the distribution of frequency ,provide a theoretical basis for the prevention and treatment of COPD. Methods Polymerase chain reaction and DNA sequencing tech-nology,electrophoresis separation method were applied to detect Q-1 and T1 locus polymorphism in ADAM33 gene. Results The genotype distribution of Q-1 and T1 locus in the case group and the control group of ADAM33 gene were in accordance with the Hardy-Weinberg equilibrium law and ADAM33 gene Q-1,T1 locus were C and T alleles. There was no significant difference in genotype and allele frequency distribution between the case group with control group,and COPD complicated with chronic respiratory failure(COPD)and hypoxemia(P > 0.05). T1(83 bp,112 bp)at a high probability of two heterozygous in the same samples(18/19),and is located in the encoding region. Conclusion No association was found between Q-1,T1 locus polymorphism in ADAM33 gene and chronic obstructive pulmonary disease in Han population in northern Guizhou.
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This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.
Subject(s)
Humans , Child , ADAM Proteins/genetics , Asthma/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Risk FactorsABSTRACT
ADAM33 es una metaloproteinasa de la matriz extracelular involucrada en la remodelación tisular y, por ello, en el asma y la enfermedad pulmonar obstructiva crónica (EPOC). Se han reportado varios polimorfismos del gen de ADAM33 asociados a la actividad enzimática. Los polimorfismos más estudiados son el V4, citosina por una guanina en la región 3 UTR, y el T1, adenina por una guanina en el exón 19 del gen. El objetivo del presente trabajo fue determinar la posible asociación de los polimorfismos de nucleótido simple de ADAM33, V4 y T1, con la presencia de asma o EPOC en pacientes venezolanos. Los polimorfismos V4 y T1 fueron analizados en 303 individuos (103 asmáticos, 100 EPOC, y 100 controles) mediante PCR-RFLP (reacción en cadena de la polimerasa y análisis de polimorfismos por longitud de fragmentos de restricción enzimática). La frecuencia genotípica del polimorfismo V4 fue significativamente mayor (p<0,05) en ambos grupos de pacientes, asmáticos y EPOC, con respecto al control. No se encontraron diferencias significativas (P=0,4) en el polimorfismo T1. Sin embargo, se evidenció una diferencia significativa (p<0,05) cuando los haplotipos y diplotipos de ADAM33 V4/T1 se compararon entre los tres grupos. Se concluye que el polimorfismo ADAM33 V4 está asociado con la presencia de asma o EPOC en pacientes venezolanos.
ADAM33 is a metalloproteinase important in the extracellular matrix for tissue remodeling, and, consequently, in asthma and chronic obstructive pulmonary disease (COPD). Several polymorphisms of the ADAM33 gene have been associated with enzyme activity. One of the most studied polymorphisms is V4, cytosine for guanine in the 3UTR region, and T1, adenine for guanine in the exon 19 of the gen. The aim of this study was to ascertain the possible association among single polymorphisms of ADAM33, V4 and T1, in Venezuelan patients with asthma or COPD. The polymorphisms V4 and T1 were analyzed in 303 individuals (103 asthmatic, 100 COPD and 100 controls) by PCR-RFLP (polymerase chain reaction and restriction fragment length polymorphisms). There was a significant difference (P<0.05) in the frequency of ADAM33 V4 polymorphism in both, asthmatic and COPD patients groups, as compared to controls. No significant differences (P=0.4) were found for T1 polymorphism. However, there were significant differences (P<0.05) when haplotypes and diplotypes of ADAM33 V4/T1 were compared in all three groups. It can be concluded that the polymorphism V4 of ADAM33 is associated with asthma or COPD in Venezuelan patients.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Asthma/genetics , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/genetics , ADAM Proteins/genetics , VenezuelaABSTRACT
Objective To investigate the correlation between ADAM33 T1, S2 gene polymorphism and Bronchial asthma risk in china. Methods We retrived the relevant published studies about ADAM33 T1, S2 gene polymorphism and bronchial asthma risk. Then we divided the population into Chinese and other Asian population. Odds ratio (OR) of Case group and control group was selected as the effect index. Stata 11.0 software was used to calculate heterogeneity test, ORs and 95%CI of two areas, and gave the forest plot and funnel plot of meta results. Results A total of 27 studies were included in this analysis,18 studies in ADAM33 T1 site were 3881 cases in case group, and 3780 cases in control group;and 14 studies in ADAM33 S2 site were 3222 cases in case group, and 3513 cases in control group. Additive model, dominant model, recessive model of ADAM33 T1 in Chinese had association with the susceptibility of bronchial asthma. The results were OR=1.488, 95% CI:1.002-2.167 in Additive model, OR=1.619, 95%CI:1.059-2.475 in dominant model;OR=2.523, 95%CI:1.910-3.333 in recessive model. Three models of ADAM33 T1 in other Asian country had no association with the susceptibility of Bronchial Asthma. Three gene model of ADAM33 S2 in Asian had no association with bronchial asthma susceptibility. Except ADAM33 T1 polymorphism in recessive model, other mode of T1, S2 had no publication bias in Chinese population. Conclusion There are association between ADAM33 T1 gene polymorphism and bronchial asthma, but ADAM33 S2 gene polymorphism and bronchial asthma have no association in Chinese population.
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Objective:To investigate the relationship between ADAM 33 polymorphisms and susceptibility of asthma of Chinese in Qingdao.Methods: The polymorphism of ADAM33 gene, they were rs2280090, rs487377 and rs2787094, were detected with SnaPshot method.Results: There was no significant difference between asthma group and control group in genotypic frequencies.Conclusion:The study shows that the rs 2280090 , rs487377 and rs2787094 were not associated with susceptibility of asthma in Han nationality in Qingdao .
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Objective To explore the correlation between ADAM33 SNP and asthma in Uygur and Han children in Urumqi. Methods Eighty-six Uygur and 111 Han children aged 3-15 years old who had asthma and lived in Urumqi were included. Meanwhile 56 Uygur and 64 Han healthy children were also included as control group. Genotyping of single nucleotide polymorphism (SNP) of V4 and T2 loci in ADAM 33 gene was performed by PCR, and verifications was made. Results There were statistical differences of V4 and T2 loci in ADAM 33 gene among asthma group and control group (P all??0.05) while there were differences in Uygur children (P all
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Objective To explore the relationship of the ADAM33 gene Q-1,T2 single nucleotide polymorphism (SNP) and suffering from chronic obstructive pulmonary disease (COPD) in Xinjiang Kazakh and Han population. Methods Peripheral blood samples to extract DNA, and the single nucleotide polymorphisms of Q-1 and T2 in ADAM33 gene were detected by SNaPshot SNP genotyping. Results Case group compared with the control group, frequencies of Q-1 locus genotypes and alleles were significant differences in Kazak (P 0.05). There were no significant differences in T2 locus genotypes and clinical indicators of lung function FEV1% predicted and FEV1/FVC in patient group (P > 0.05). Conclusion The ADAM33 gene Q-1 locus may be related to the COPD susceptibility in Xinjiang Kazak, Han.
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Objective To explore correlation of Xinjiang Kazakh population who suffered from COPD with polymor?phisms of F+1,S2,T1,ST+5 locus of ADAM33 gene. Methods Blood samples (n=193) from healthy controls (Control group, n=193) and COPD patients (Case group, n=197) were detected by SNP SNaP shot. Results Comparing case group with the control group, gene frequency and allele frequency of F+1 locus were of significant differences (P0.05). The gene frequencies and allele frequency of S2、T1 and ST+5 locus were not significantly differ?ent between case group and control group (P>0.05). F+1 and S2 locus were analyzed by haplotype analysis which showed that there was significant differences in Hap1 (CC) haplotype between case group and control group (P1 revealed that its haplotype may increase the risk of COPD . The distri?bution of Hap2 (TG) and Hap4 (CG) were not significantly different (P>0.05) between the 2 groups. T1 and ST+5 locus were analyzed by haplotype analysis which showed significant differences in haplotypes between case group and control group (P<0.05). Conclusion The occurrence of COPD may be related to the polymorphism of ADAM33 gene in F+1 locus in Xinjiang Kazakh.
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Objective To investigate the association between polymorphism of S1, S2 locus allele in ADAM 33 gene and chronic obstructive pulmonary disease (COPD) and lung function in Xinjiang Uygur population. Methods Blood sam?ples from 217 COPD patients and 218 healthy controls were collected. Samples of DNA was extracted, and S1, S2 single nu?cleotide polymorphism (ADAM 33) was detected by ABI SNaPshot SNP genotyping. Results There were no significant dif?ferences in the frequencies of S1 locus CC, CT, TT genotypes and C, T alleles between patient group and control group (P>0.05). There were no significant differences in the frequencies of S1 locus CC, CG, GG genotypes and C, G alleles between patient group and control group (P>0.05). In patient group, there were no significant differences in S1, S2 locus genotype and clinical indicators of lung function display, and in the FEV1%predicted and FEV1/FVC (P>0.05). Haplotype analysis showed that there were no significant differences in three kinds of haplotypes between patient group and control group ( P>0.05). Conclusion There is no significant difference in the polymorphism of S1, S2 locus allele in ADAM 33 gene and the susceptibility to COPD in Xinjiang Uygur population.
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Background & objectives: ADAM33 is a member of a family of genes that encode membrane-anchored proteins with a disintegrin and a metalloprotease domain, primarily expressed in lung fibroblasts and bronchial smooth muscle cells. ADAM33 has been identified as a risk factor for asthma and is known as a gene associated with airway remodelling. The present study was conducted with the aims to investigate the expression of ADAM33 protein in patients of asthma and non-asthmatic controls, and to assess if the expression of ADAM33 protein relates with severity of asthma. Methods: A total of 35 subjects, including 27 patients with asthma and eight non-asthmatic controls were included using Global Initiative for Asthma guidelines 2005. Bronchial biopsy tissues were collected and paraffin sections were made to store all study samples. Immunohistochemistry was performed using standardized protocol. Results: An increase in expression of ADAM33 protein was observed in the epithelium, smooth muscle and mesenchymal cells of asthma cases when compared to controls but there was no relationship with severity of asthma. Interpretation & conclusions: A higher expression of ADAM 33 protein was seen in asthma patients compared to controls. Large prospective studies need to be done with adequate study design to confirm these preliminary finding.
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The original concept of asthma being primarily a disease of airways smooth muscle drove the development of bronchodilator drugs. However when it was realised that airway inflammation underpinned the disordered airway function, this gave way to the development of controller therapies such as inhaled cromones and corticosteroids. More recently the discovery of complex interconnecting cytokine and chemokine networks has stimulated the development of biologics with varying success. With the recognition that airway wall "remodelling" is present early in asthma inception and is in part driven by aberrant epithelial-mesenchymal communication both genetic and environmental factors beyond allergen exposure such as virus infection and air pollution are being seen as being increasingly important not only in asthma exacerbations but in the origins of asthma and its evolution into different sub-phenotypes. This brings us round full circle to once again considering that the origins of asthma lie in defects in the formed elements of the airway; the epithelium, smooth muscle, and vasculature. Over the last 25 years Professor You Young Kim has engaged in the exciting discovery science of allergy and asthma and has made an enormous contribution in bringing Korea to the forefront of disease management and research, a position that both he and his colleagues can justly be proud of.
Subject(s)
Adrenal Cortex Hormones , Air Pollution , Airway Remodeling , Asthma , Disease Management , Epithelium , Hypersensitivity , Inflammation , Korea , Muscle, Smooth , VirusesABSTRACT
OBJETIVO: Verificar, em uma amostra de pacientes com asma atópica persistente leve, moderada e grave, a associação entre os polimorfismos dos genes fator de crescimento transformante-beta1 (TGF-beta1) (C-509T e T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) e ADAM33 (S_2) com a gravidade da asma. MÉTODOS: Realizou-se um estudo clínico laboratorial prospectivo em pacientes com asma atópica persistente, comparados a um grupo controle no Hospital Universitário da Universidade Estadual de Campinas nos anos de 2006 e 2007. A análise do polimorfismo T869C do gene TGF-beta1 foi realizada pela técnica de reação em cadeia da polimerase (PCR) + sistema de amplificação refratária de mutação (ARMS). Os outros polimorfismos, C-509T do gene TGF-beta1, C-159T do gene CD14, C-590T da IL-4, ILe50Val da IL-4Ra e S2 do gene ADAM33, foram detectados por PCR e enzima de restrição. RESULTADOS: Foram incluídos 88 pacientes com asma atópica persistente (27 leves, 23 moderados e 38 graves) e 202 indivíduos saudáveis, doadores de sangue. Em relação ao polimorfismo T869C (TGF-beta1), observou-se uma associação entre o genótipo CC e os pacientes com asma grave. Nenhuma associação foi encontrada com os polimorfismos C-509T (TGF-beta1), C-590T (IL4) e S_2 (ADAM33). Quando se comparou a distribuição da freqüência genotípica do polimorfismo C-159T (CD14) na asma grave com o grupo controle, foi observado um resultado significativo com o genótipo TT. Houve associação significativa do genótipo Val/Val (IL-4R) com a asma leve. CONCLUSÃO: Nossos resultados indicam que os polimorfismos T869C (TGF-beta1), C-159T (CD14) e Val/Val (IL-4R) podem estar envolvidos na modulação da gravidade da asma.
OBJECTIVE: To verify the association of transforming growth factor-beta1 (TGF-beta1) (C-509T and T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) and ADAM33 (S_2) gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe persistent atopic asthma. METHODS: A clinical, laboratory, prospective study was performed in patients with persistent atopic asthma, compared to a control group at Hospital Universitário da Universidade Estadual de Campinas between 2006 and 2007. Analysis of the TGF-beta1 T869C gene polymorphism was performed using the technique polymerase chain reaction (PCR) + amplification refractory mutation system (ARMS). TGF-beta1 C-509T, CD14 C-159T, IL-4 C-590T, IL-4Ra ILe50Val, and ADAM33 S2 gene polymorphisms were detected by PCR and restriction enzyme. RESULTS: This study included 88 patients with persistent atopic asthma (27 mild, 23 moderate and 38 severe) and 202 healthy blood donors. As to T869C polymorphism (TGF-beta1), there was an association between the CC genotype and patients with severe asthma. There was no association in polymorphisms C-509T (TGF-beta1), C-590T (IL-4) and S_2 (ADAM33). When distribution of C-159T polymorphism genotype frequency (CD14) in severe asthma was compared with the control group, there was a significant result with the TT genotype. There was significant association of the Val/Val genotype (IL-4R) with mild asthma. CONCLUSION: Our results indicate that T869C (TGF-beta1), C-159T (CD14) and Val/Val (IL-4R) polymorphisms might be involved in modulation of asthma severity.