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At least 19 recordsLinked to original sources
PubMed1985

A necropsy study of Pi phenotypes, emphysema, and smoking.

Pi phenotypes, determined post mortem by isoelectric focusing and immunofixation, emphysema, assessed from inflation fixed specimens and smoking history were correlated in 186 hospital necropsies. It was possible to determine Pi phenotype in 98.4% of the specimens. Phenotype M occurred in 87.5%, MZ in a 8.1%, MS in 2.1% and FM in 0.5%. An expected association was found between smoking and emphysema but not between the Pi phenotypes and emphysema. Thus, while smoking is a major aetiological factor, the Pi MZ heterozygous state does not seem to predispose to structural emphysema. However, the small number of cases did not allow an estimation of the risk of smoking in Pi MZ heterozygous persons compared to those with the normal Pi phenotype.

Adult↗
PubMed2026

Influence of FAM13A gene polymorphism and serum matrix metalloproteinases 9 and 12 on the phenotypes of chronic obstructive pulmonary disease.

PURPOSE: FAM13A as a susceptibility gene for chronic obstructive pulmonary disease(COPD).Many studies verified that FAM13A involved epithelial‒mesenchymal transition (EMT) via the TGF-β1 pathway, some accompanied by an increase in MMP levels. The present study aimed to explore the disease susceptibility of the FAM13A gene, with clinical phenotypes, and investigate the relationships between FAM13A SNP loci and the serum levels of MMP-9 and MMP-12. PATIENTS AND METHODS: We recurited 497 patients with stable COPD patients and 303 healthy controls. Data on blood tests, pulmonary function, and HRCT imaging were collected. Serum MMP-9 and MMP-12 levels were measured by ELISA. Genomic DNA was extracted, and SNPs in the FAM13A gene were detected using targeted region genotyping chips. Logistic regression analysis was performed to assess the associations between SNP loci and COPD susceptibility. Differences in pulmonary function, haematological indicators, bronchial wall thickness, and emphysema parameters among different genotypes were evaluated. Multiple linear regression analysis was used to explore the relationship between genotypes and serum MMP-12 level. RESULTS: We screened a total of 476 SNPs and identified the rs2869947 polymorphism in the FAM13A gene as significantly associated with an increased risk of COPD,Stratified analyses further revealed that this association was particularly in males and individual with BMI ≥ 24.Serum levels of MMP-9 and MMP-12 were significantly higher in COPD patients compared with healthy controls. Genotype(AA vs.GG) showed no significant association with pulmonary function severity,bronchial wall indices,hematological marker,and serum MMP-9 levels in COPD patients(P > 0.05).Compared with GG genotype, AA genotype presented significantly higher LAA-950% and serum MMP-12 levels (P = 0.049 and P = 0.023). CONCLUSION: Our findings suggest that the FAM13A SNP rs2869947 may be associated with COPD susceptibility in the Han Chinese population. The FAM13A AA genotype increased serum MMP-12 levels and correlated with emphysema phenotype.

Humans↗
PubMed1990

Biochemical intermediates in alpha 1-antitrypsin deficiency: residual family resemblance for total alpha 1-antitrypsin, oxidized alpha 1-antitrypsin, and immunoglobulin E after adjustment for the effect of the Pi locus.

alpha 1-antitrypsin (alpha 1 AT) deficiency is variably associated with the development of pulmonary emphysema. To gain insight into the process which begins the Z point mutation at the Protease Inhibitor (Pi) locus and results in the variable development of emphysema, three quantitative phenotypes, including total alpha 1 AT, oxidized alpha 1 AT, and total immunoglobulin E (IgE), were measured in sera from alpha 1-antitrypsin-deficient individuals and their families. The mean and variance effects of the Pi locus on these biochemical phenotypes were removed, and path analysis of the residual phenotypes was performed by using a TAU model to investigate whether there was any additional multifactorial transmission. Significant transmission was demonstrated for total serum IgE and serum-oxidized alpha 1 AT, which could be due to major genes other than the Pi locus, polygenes, or familial environment. Segregation analysis of the residual phenotypes was performed to determine whether additional major gene effects, other than the Pi effect, influence these quantitative phenotypes. Convincing evidence for an additional major gene was not found for oxidized alpha 1 AT, total alpha 1 AT, or IgE.

Data Interpretation, Statistical↗
PubMed1990

Alpha-1-antitrypsin deficiency in a large sibship.

We studied alpha 1-antitrypsin deficiency in a large family of 10 siblings: 3 subjects had PiZZ phenotype, but only 1 had emphysema; 2 subjects had no respiratory complaint. The patient with emphysema was a heavy smoker. According to the literature, this case suggests that, in PiZZ phenotype, emphysema appears earlier and is more severe if the patients smoke.

Adult↗
PubMed1989

Alpha 1-antitrypsin deficiency caused by the alpha 1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha 1-antitrypsin gene incapable of producing alpha 1-antitrypsin.

alpha 1-Antitrypsin (alpha 1AT) deficiency is a hereditary disorder associated with reduced serum alpha 1AT levels and the development of pulmonary emphysema. An alpha 1AT gene is defined as "Null" when no alpha 1AT in serum is attributed to that alpha 1AT gene. Although all alpha 1AT Null genes have identical phenotypic consequences (i.e. no detectable alpha 1AT in the serum), different genotypic mechanisms can cause the Null state. This study defines the molecular basis for the alpha 1AT gene Nullmattawa, identified and cloned from genomic DNA of an individual with the Null-Null phenotype and emphysema resulting from the heterozygous inheritance of the Nullmattawa and Nullbellingham genes. Sequencing of exons Ic-V and all exon-intron junctions of the Nullmattawa gene demonstrated it was identical to the common normal M1(Val213) alpha 1AT gene except for the insertion of a single nucleotide within the coding region of exon V, causing a 3' frameshift with generation of a premature stop signal. Family analysis using oligonucleotide probes specific for the Nullmattawa sequence demonstrated the gene was inherited in an autosomal fashion. Examination of blood monocytes demonstrated that a normal-sized, 1.8-kb alpha 1AT mRNA transcript is associated with the Nullmattawa gene and in vitro translation of mRNA with the Nullmattawa mutation showed it translated at a normal rate but produced a truncated alpha 1AT protein. Additionally, retroviral transfer of the alpha 1AT Nullmattawa cDNA to murine fibroblasts demonstrated no detectable intracellular or secreted alpha 1AT, despite the presence of alpha 1AT Nullmattawa mRNA transcripts. These findings are consistent with the concept that the molecular pathophysiology of Nullmattawa is likely manifested at a posttranslational level. The identification of the Nullmattawa gene supports the concept that Null alpha 1AT alleles represent a heterogenous group in which very different mechanisms cause the identical phenotypic state.

Adult↗
PubMed1988

Intravenous administration of alpha-1-proteinase inhibitor in patients of PiZ and PiM phenotype. Preliminary report.

Nine patients with moderate pulmonary emphysema, six of PiZ phenotype and three of PiM phenotype, have received a single intravenous infusion of alpha-1-proteinase inhibitor (human) (A1PI), in a dose of 60 mg/kg over a 30-minute period. They also received a tracer dose (300 microCi) of 131I-labeled A1PI. No active or passive immunization against hepatitis was given. No acute toxicity was observed. Compared with baseline data, significant elevations of serum A1PI (measured both antigenically and as anti-elastase activity) occurred, with a serum half-life approximating 110 hours. Bronchoalveolar lavage fluid, obtained 48 hours after infusion, reflected a significant increase in A1PI concentration versus baseline bronchoalveolar lavage fluid values. Serial gamma camera images of the lungs confirmed persistence of enhanced lung radioactivity for several days. Urinary desmosine excretion did not change following A1PI infusion. During the period of follow-up thus far, no patient has had chronic toxicity, results of liver function tests have been stable, and there has been no development of hepatitis B antigen or antibodies to hepatitis B surface or core antigens.

Adult↗
PubMed1979

[Laboratory procedures in the detection of deficiencies and the determination of alpha 1-antitrypsin phenotypes in the blood serum].

Eriksson's method was analysed and an attempt was made to determine the probability of the occurrence of phenotypes predisposing to emphysema and obstructive catarrhs, when low alpha-1-AT values were found using gelatinous film or immunochemical methods. The authoresses propose a three-stage system for the detection of all those susceptible to emphysema.

Humans↗
PubMed1985

Urinary excretion of desmosine (elastin cross-links) in subjects with PiZZ alpha-1-antitrypsin deficiency, a phenotype associated with hereditary predisposition to pulmonary emphysema.

To evaluate the concept that lung elastin degradation is accelerated in homozygous alpha-1-antitrypsin (AAT) deficient persons, we prepared acid hydrolysates of urine and used a radioimmunoassay for desmosine to measure urine concentrations of this elastin-specific cross-link in such persons and in control subjects. Excretion of desmosine in 17 homozygous AAT-deficient (PiZZ) patients with emphysema was compared with that in 27 patients with interstitial lung diseases (16 sarcoid, 5 idiopathic pulmonary fibrosis, 6 other interstitial lung diseases) and 26 healthy subjects. Both smokers and nonsmokers were present in all groups. Urinary desmosine concentration (microgram/100 mg creatinine) was 2.35 +/- 0.93 in the PiZZ patients, 2.49 +/- 1.01 in those with interstitial lung disease, and 2.05 +/- 0.54 in the healthy control subjects (p greater than 0.1, all comparisons). Because abnormal pulmonary elastolysis may be largely completed before symptoms of emphysema develop in AAT-deficient persons, we also tested 6 asymptomatic adults with homozygous AAT deficiency (PiZZ) and 5 PiZZ children. Urine desmosine (microgram/100 mg creatinine) was not significantly elevated in either group compared with that in the age-matched control subjects, although children (PiZZ and age-matched controls) showed higher excretions than did adults (6 asymptomatic PiZZ adults, 2.60 +/- 0.91; 5 PiZZ children, 3.27 +/- 0.62; 10 control children, 3.61 +/- 0.62). These data suggest that pathologic lung elastolysis in the PiZZ subject may constitute too small a fraction of total-body elastin turnover to be detected by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

[Pan-lobular emphysema: relationship with serum alpha-1-antitrypsin levels, Pi phenotype and the HLA system (author's transl)].

Pi phenotypes have been studied in a group of 433 patients. Patients with panacinar emphysema and/or bullae were identified from careful analysis of their clinical, physiological, radiological and anatomical characteristics. Twenty-five p.cent of the emphysematous patients were MZ; there was no significant difference in the alpha-1-antitrypsin plasmatic levels between the groups. The HLA antigens were studied in order to try to identify the possible cofactors in the development of emphysema. The role of occupational pollutants and/or of tobacco is discussed. The frequency of the MZ phenotype in our series differs from previous publications. This discrepancy is discussed on the basis of the criterious used to identify the emphysematous patients.

Blister↗
PubMed1985

Emphysema, cirrhosis, and heart block in a young patient with partial alpha 1 antitrypsin deficiency (PiMZ phenotype).

Severe lung disease and liver disease are not recognised features of the PiMZ phenotype, which is associated with alpha 1 antitrypsin deficiency. A 31 year old woman with this phenotype was found to have emphysema and complete heart block and showed evidence of hepatic cirrhosis, although her three sisters, all of whom had the same phenotype, were clinically normal. This case supports the possibility of a causal relation between the PiMZ phenotype and chronic lung and liver disease, but an association between alpha 1 antitrypsin deficiency and complete heart block could not be proved in this patient.

Adult↗
PubMed1979

Assessment of alpha-1-antitrypsin deficiency heterozygosity as a risk factor in the etiology of emphysema. Physiological comparison of adult normal and heterozygous protease inhibitor phenotype subjects from a random population.

For plethysmographic studies of lung mechanics and measurement of pulmonary diffusing capacity, 62 subjects were drawn from a randomly selected population sample. Data obtained from the 24 subjects of heterozygous phenotype for alpha-1-antitrypsin deficiency (PiMZ) were compared by age group with data from 38 normal (PiM) subjects matched for sex, age, and smoking history. Comparison of mean values by age group for lung volumes, diffusing capacity, lung elastic recoil, maximum expiratory flow, and the occurrence of frequency dependence of dynamic compliance revealed no differences between phenotype groups. There was no evidence of an accelerated effect of aging among PiMZ subjects when compared with normal counterparts nor was there evidence of an increased effect of smoking. From these data it appears that the PiMZ phenotype per se is not a risk factor in the development of emphysema.

Adult↗
PubMed1974

Alpha-1-antitrypsin deficiency in pulmonary and liver degeneration.

The characteristics of emphysema and cirrhosis in Pi ZZ (alpha-1-antitrypsin deficiency) and SZ patients are reviewed. The clinical and laboratory data have been incorporated into a simple hypothesis on the development of these diseases. The PiZ protein can not be secreted normally from the liver cells. The accumulation of alpha-1-antitrypsin in the liver may result in cirrhosis, and the deficiency in serum to emphysema.

Humans↗