Influence of deficient α1-anti-trypsin phenotypes on clinical characteristics and severity of asthma in adults

Miravitlles, Marc; Vilà, Sara; Torrella, M.; Balcells, Eva; Rodríguez‐Frías, Francisco; Roza, Cristian de la; Jardí, R.; Vidal, Rafael

doi:10.1053/rmed.2001.1237

Cited by 37 publications

(22 citation statements)

References 20 publications

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“…Aderele et al [18] reported that the serum levels of α 1 AT in asthmatic children were significantly lower in controls ( P < 0.02). We have observed a decreased α 1 AT activity in patients of asthma and these results are in agreement with other studies carried by various workers [9, 17, 18]. …”

Section: Discussionsupporting

confidence: 93%

“…The earlier studies correlating the asthma features and α 1 AT levels have shown variable observations. A study conducted by Miravitlles et al demonstrated that 22 out of 111 (19.8%) of asthmatics with a deficient phenotype of α 1 AT gene had normal values of α 1 AT [17]. Also, no significant differences were found when α 1 AT values were compared with each of the asthma patient groups classified according to severity criteria [17].…”

Section: Discussionmentioning

confidence: 99%

“…A study conducted by Miravitlles et al demonstrated that 22 out of 111 (19.8%) of asthmatics with a deficient phenotype of α 1 AT gene had normal values of α 1 AT [17]. Also, no significant differences were found when α 1 AT values were compared with each of the asthma patient groups classified according to severity criteria [17]. Eden et al had reported that 38% of subjects, having asthma with PIZZ genotype, had very low levels of α 1 AT in their sera [9].…”

Section: Discussionmentioning

confidence: 99%

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Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma

Kumar

Bhadoria

Dutta

et al. 2012

Comparative and Functional Genomics

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Asthma has been an inflammatory disorder accompanied by tissue remodeling and protease-antiprotease imbalance in lungs. The SNPs of alpha-1 antitrypsin (α 1 AT) and tissue inhibitor of metalloproteinase-1 (TIMP-1) genes were studied for their association with asthma. Genotyping of α 1 AT and TIMP-1 genes was performed in 202 asthmatics and 204 controls. Serum levels of α 1AT, TIMP-1 and cytokines were estimated to find if the interplay between genotypes and cellular biomarkers determines the pathogenesis of asthma. The analysis of results showed significantly low level of α 1AT in the serum of asthmatics as compared to controls (P = 0.001), whereas cytokines were elevated in patients. No significant difference was observed in the concentration of TIMP-1 in patients and controls. Genotyping led to the identification of 3 SNPs (Val213Ala, Glu363Lys, and Glu376Asp) in α 1 AT gene. The novel SNP Glu363Lys of α 1 AT was found to be associated with asthma (P = 0.001). The analysis of TIMP-1 gene showed the occurrence of seven SNPs, including a novel intronic SNP at base G3774A. The allele frequency of G3774A and Phe124Phe was significantly higher in asthmatics as compared to controls. Thus, the SNP Glu363Lys of α 1 AT and G3774A and Phe124Phe of TIMP-1 could be important genetic markers for use in better management of the disease.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma

Kumar

Bhadoria

Dutta

et al. 2012

Comparative and Functional Genomics

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“…(29) Other studies, however, found no relationship between heterozygous phenotypes and clinical or functional changes in asthma patients. (30) There seem to be a relationship between occupational exposure to particulate inhalants and the development of pulmonary disease in patients with the PiZZ phenotype. (31) An association between AAT deficiency and cancer, including lung cancer, has also been suggested.…”

Section: Radiological Findingsmentioning

confidence: 99%

Deficiência de alfa-1 antitripsina: diagnóstico e tratamento

et al. 2008

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Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues.Keywords: alpha 1-antitrypsin; Emphysema; Pulmonary disease, chronic obstructive. ResumoA deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnós-tico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiro...

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“…[21][22][23][24] However, patients with the PiZ allele, despite having lower values of the serum AAT than those with the wild type, this difference was not statistically significant, which might need a larger studied population to demonstrate a statistically significant difference. The AAT plasmatic concentration may vary in the patient's sample with other physiological or pathological states like age, asthma duration, an acute bronchial inflammation and/or the corticoid treatments.…”

mentioning

confidence: 99%

Αlpha-1 Antitrypsin Gene Polymorphism in the Egyptian Population: Association with Obstructive Lung Diseases

Daabis¹,

Muawia²,

Ahmed³

et al. 2014

Pulm Res Respir Med Open J

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Background: Given the potential adverse effects of asthma and Chronic Obstructive Pulmonary Disease (COPD), this study was undertaken to explore Alpha-1 Antitrypsin (AAT) polymorphism in the Egyptian population and its role in the development and/ or progression of asthma and COPD. The identification of IL-10 as a potential modifier gene for COPD susceptibility provided insight into additional inflammatory pathways to consider in AAT deficiency. Methods: This study was carried on 90 unrelated Egyptians; 37 asthmatics, 33 COPD patients and 20 controls. Patients were evaluated clinically and with spirometry. The frequency of AAT gene polymorphism was assessed by real-time PCR. Serum levels of AAT protein, IL-10 and IgE were estimated. Results: PiZ allele was found in COPD and asthma patients as well as controls. While PiS allele was never shown up in all the groups. The prevalence of PiZ was higher in asthma and COPD than in controls (75.75%, 72.7% and 50% respectively). Serum AAT was significantly decreased in patients with asthma and COPD. Patients with the PiZ allele, despite having lower values of the serum AAT, this difference was not significant. Serum AAT was significantly correlated with severity of airflow obstruction in both asthma and COPD. There was a significant elevation of serum IgE in COPD patients carrying PiZ allele. Serum IL-10 was significantly higher in asthma and COPD patients than the controls. There was a positive significant correlation between IL-10 and IgE in COPD patients. Conclusion: The z allele frequency in the Egyptian population is higher among asthmatic and COPD patients, suggesting that it could in fact be an underlying hidden risk factor for the development of these diseases. Asthmatics carrying this deficient allele have a genetic predisposition for progressing to COPD. Genetic counselling of patients having obstructive airway diseases is very important for diagnosis, prognosis and treatment.

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Influence of deficient α1-anti-trypsin phenotypes on clinical characteristics and severity of asthma in adults

Cited by 37 publications

References 20 publications

Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma

Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma

Deficiência de alfa-1 antitripsina: diagnóstico e tratamento

Αlpha-1 Antitrypsin Gene Polymorphism in the Egyptian Population: Association with Obstructive Lung Diseases

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Influence of deficient α1-anti-trypsin phenotypes on clinical characteristics and severity of asthma in adults

Cited by 37 publications

References 20 publications

Theα1ATandTIMP-1Gene Polymorphism in the Development of Asthma

Theα1ATandTIMP-1Gene Polymorphism in the Development of Asthma

Deficiência de alfa-1 antitripsina: diagnóstico e tratamento

Αlpha-1 Antitrypsin Gene Polymorphism in the Egyptian Population: Association with Obstructive Lung Diseases

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Product

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Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma

Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma