scholarly journals Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

2016 ◽  
Vol 42 (5) ◽  
pp. 311-316 ◽  
Author(s):  
Rodrigo Russo ◽  
Laura Russo Zillmer ◽  
Oliver Augusto Nascimento ◽  
Beatriz Manzano ◽  
Ivan Teruaki Ivanaga ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Cross Sectional Study ◽  
Genotype Distribution ◽  
Cross Sectional ◽  
Serpina1 Gene ◽  
Copd Patients ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients.

Alpha-1 Antitrypsin Deficiency in COPD Patients: A Cross-Sectional Study

2015 ◽  
Vol 51 (11) ◽  
pp. 539-543 ◽  
Author(s):  
Patricia Beatriz Sorroche ◽  
Mariano Fernández Acquier ◽  
Orlando López Jove ◽  
Eduardo Giugno ◽  
Salvador Pace ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Copd Patients ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals Comparison of COVID-19 outcomes with alpha-1-antitrypsin deficiency prevalence: A cross-sectional study.

2021 ◽  
Author(s):  
Yılmaz Sezgin ◽  
Sinan Becel
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Significant Relationship ◽  
Linear Regression Analysis ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Background: We hypothesized that the geographic distributions of COVID-19 prevalence and risky alpha-1-antitrypsin allele prevalence are similar. We aimed to investigate whether there is a relationship between the geographical density of the COVID-19 pandemic and the distributions of risky alpha-1-antitrypsin alleles. Methods: This research is a cross-sectional study. Alpha-1-antitrypsin PI*SZ and PI*ZZ genotypes frequencies of European and American countries were compared with the case and death data related to the COVID-19 pandemic as of March 30, 2021. The relationship between the data was evaluated using Linear regression analysis. Results: According to the linear regression analysis results, a significant relationship was found between the number of COVID-19 cases in both European and American countries and the sum of PI*SZ and PI*ZZ genotypes. Similarly, according to the linear regression analysis results, a significant relationship was found between the COVID-19 death numbers in both European and American countries and the sum of PI*SZ and PI*ZZ genotypes. Conclusions: The findings showed that the prevalence distribution of the risky alleles of the gene defect that causes alpha-1-antitrypsin insufficiency is related to the prevalence of COVID-19 pandemic data.

Characterization of the Serum a1-Antitripsine Level in Primary Spontaneous Pneumotorax Patients

2018 ◽  
Vol 69 (9) ◽  
pp. 2591-2593
Author(s):  
Cristina Grigorescu ◽  
Liviu Ciprian Gavril ◽  
Laura Gavril ◽  
Tiberiu Lunguleac ◽  
Bogdan Mihnea Ciuntu ◽  
...  
Keyword(s):  
Serum Level ◽  
Pulmonary Emphysema ◽  
Spontaneous Pneumothorax ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Determining Factor

Diagnosis of primary or idiopathic spontaneous pneumothorax is one of exclusion, and in fact defines an entity that may have a difficult or impossible cause to be highlighted by current means, we consider it appropriate to study these etiopathogenic aspects. There is a definite association between alpha-1 antitrypsin deficiency and pulmonary emphysema and indirect spontaneous pneumothorax secondary to an emphysematous pulmonary lesion. Dose of alpha-1 antitrypsin is an immunoturbinimetric method for in vitro determination of alpha-1 antitrypsin in human serum and plasma. This product is calibrated to be used for the Daytona RX analyzer. The serum level of alpha-1-antitrypsin is not a determining factor in the postoperative evolution characterized by the interval until air loss disappears, but certainly exerts some influence, the exact level of which remains to be determined.

scholarly journals Association between circulating alpha-1 antitrypsin polymers and lung and liver disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alexa Núñez ◽  
Irene Belmonte ◽  
Elena Miranda ◽  
Miriam Barrecheguren ◽  
Georgina Farago ◽  
...  
Keyword(s):  
Liver Disease ◽  
Genetic Diseases ◽  
Sandwich Elisa ◽  
Liver Stiffness ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cross Sectional ◽  
Impaired Lung Function ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Abstract Background Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. Method This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. Results A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). Conclusions Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.

Differences in training response between patients with alpha-1 antitrypsin deficiency and COPD patients

2015 ◽  
Author(s):  
Inga Heinzelmann ◽  
Sebastian Gehlert ◽  
Tobias Welte ◽  
Wilhelm Bloch ◽  
Sabina Janciauskiene ◽  
...  
Keyword(s):  
Copd Patients ◽  
Training Response ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Natural Progression of Alpha-1 Antitrypsin Deficiency Among Hospitalized COPD Patients in the US

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 497A
Author(s):  
Christopher Blanchette ◽  
Joshua Noone ◽  
Debosree Roy ◽  
Bryce Van Doren ◽  
Emily Zacherle ◽  
...  
Keyword(s):  
Copd Patients ◽  
Natural Progression ◽  
The Us ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Cluster Headache and Alpha 1-antitrypsin Deficiency

Cephalalgia ◽  
2009 ◽  
Vol 30 (1) ◽  
pp. 113-117 ◽  
Author(s):  
O Summ ◽  
N Gregor ◽  
M Marziniak ◽  
I Gralow ◽  
IW Husstedt ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Sleep Apnoea ◽  
Primary Headaches ◽  
Wild Type ◽  
Attack Frequency ◽  
Serpina1 Gene ◽  
Significant Difference ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Little is known about the pathophysiology of cluster headache (CH), one of the most debilitating primary headaches. Interestingly, associations of lung affecting diseases or lifestyle habits such as smoking and sleep apnoea syndrome and CH have been described. Certain genotypes for alpha 1-antitrypsin (α1-AT) are considered risk factors for emphysema. Our aim was to investigate possible associations between common genotypes of the SERPINA1 gene and CH. Our study included 55 CH patients and 55 controls. α1-AT levels in serum and the genotype were analysed. Patients CH characteristics were documented. We could not detect any association between CH and a genotype that does not match the homozygous wild type for α1-AT. Interestingly, there is a significant difference of CH attack frequency in patients who are heterozygous or homozygous M allele carriers. We conclude that the presence of an S or Z allele is associated with higher attack frequency in CH.

scholarly journals Small molecule screen employing patient-derived iPS hepatocytes identifies LRRK2 as a novel therapeutic target for Alpha1 Antitrypsin Deficiency

2021 ◽  
Author(s):  
Deniz Kent ◽  
Soon Seng Ng ◽  
Payam Khoshkenar ◽  
Adam M. Syanda ◽  
Li Chao Zheng ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Kinase Inhibitors ◽  
Fibrotic Liver ◽  
Serpina1 Gene ◽  
Antitrypsin Deficiency ◽  
Threatening Condition ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Lrrk2 Kinase ◽  
Alpha 1 Antitrypsin ◽  
Fibrotic Liver Disease

Alpha-1 antitrypsin deficiency is a life-threatening condition caused by inheritance of the SERPINA1 gene Z variant. This single base pair mutation leads to protein misfolding, ER entrapment and gain of toxic function. Despite the significant unmet medical need presented by this disorder, there remain no approved medicines and the only curative option is liver transplantation. We hypothesized that an unbiased screen of human hepatocytes harbouring the Z mutation (ATZ) using small molecules targeted against protein degradation pathways would uncover novel biological insights of therapeutic relevance. Here we report the results of that screen performed in a patient-derived iPSC model of ATZ. Starting from 1,041 compounds we identified 14 targets capable of reducing polymer burden, including Leucine-rich repeat kinase-2 (LRRK2), a well-studied target in Parkinsons. Genetic deletion of LRRK2 in ATZ mice reduced polymers and associated fibrotic liver disease leading us to test a library of commercially available LRRK2 kinase inhibitors in both patient iPSC and CHO cell models. One of the molecules tested, CZC-25146, reduced polymer load, increased normal AAT secretion and reduced inflammatory cytokines with pharmacokinetic properties supporting its potential use for treating liver diseases. We therefore tested CZC-25146 in the ATZ mouse model and confirmed its efficacy for polymer reduction without signs of toxicity. Mechanistically, in both human and mouse models, our data show CZC-25146 inhibits LRRK2 kinase activity and induces autophagy. Cumulatively, these findings support the use of CZC-25146 and LRRK2 inhibitors in general in hepatic proteopathy disease research and as potential new treatment approaches for patients.

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