Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age...
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| Vydáno v: | Biochemia medica Ročník 24; číslo 2; s. 293 - 298 |
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| Jazyk: | angličtina |
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Croatia
Croatian Society of Medical Biochemistry and Laboratory Medicine
01.01.2014
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| ISSN: | 1846-7482, 1330-0962, 1846-7482 |
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| Abstract | Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone.
50 unrelated patients (28 males/22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests.
AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZMmalton, 1 ZQ0amersfoort), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, Mmalton and Q0amersfoort, the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063).
There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone. |
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| AbstractList | Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone.
50 unrelated patients (28 males/22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests.
AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZMmalton, 1 ZQ0amersfoort), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, Mmalton and Q0amersfoort, the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063).
There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone. Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone.INTRODUCTIONAlpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone.50 unrelated patients (28 males/22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests.SUBJECTS AND METHODS50 unrelated patients (28 males/22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests.AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZMmalton, 1 ZQ0amersfoort), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, Mmalton and Q0amersfoort, the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063).RESULTSAATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZMmalton, 1 ZQ0amersfoort), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, Mmalton and Q0amersfoort, the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063).There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.CONCLUSIONThere is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone. |
| Author | Ljujic, Mila Radojkovic, Dragica Djordjevic, Valentina Mirkovic, Dusko Beletic, Andjelo Nagorni-Obradovic, Ljudmila Dudvarski-ilic, Aleksandra Milenkovic, Branislava Majkic-Singh, Nada |
| AuthorAffiliation | 2 School of Medicine, University of Belgrade & Clinic for Lung Diseases, Clinical Center of Serbia, Belgrade, Serbia 3 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia 5 Society of Medical Biochemists of Serbia, Belgrade, Serbia 4 Faculty of Pharmacy, University of Belgrade & Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia 1 Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia |
| AuthorAffiliation_xml | – name: 1 Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia – name: 5 Society of Medical Biochemists of Serbia, Belgrade, Serbia – name: 3 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia – name: 2 School of Medicine, University of Belgrade & Clinic for Lung Diseases, Clinical Center of Serbia, Belgrade, Serbia – name: 4 Faculty of Pharmacy, University of Belgrade & Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia |
| Author_xml | – sequence: 1 givenname: Andjelo surname: Beletic fullname: Beletic, Andjelo – sequence: 2 givenname: Aleksandra surname: Dudvarski-ilic fullname: Dudvarski-ilic, Aleksandra – sequence: 3 givenname: Branislava surname: Milenkovic fullname: Milenkovic, Branislava – sequence: 4 givenname: Ljudmila surname: Nagorni-Obradovic fullname: Nagorni-Obradovic, Ljudmila – sequence: 5 givenname: Mila surname: Ljujic fullname: Ljujic, Mila – sequence: 6 givenname: Valentina surname: Djordjevic fullname: Djordjevic, Valentina – sequence: 7 givenname: Dusko surname: Mirkovic fullname: Mirkovic, Dusko – sequence: 8 givenname: Dragica surname: Radojkovic fullname: Radojkovic, Dragica – sequence: 9 givenname: Nada surname: Majkic-Singh fullname: Majkic-Singh, Nada |
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| CitedBy_id | crossref_primary_10_1016_j_arbres_2017_05_012 crossref_primary_10_1183_13993003_00610_2017 crossref_primary_10_1016_j_arbr_2017_10_005 |
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| SubjectTerms | Adult Aged Algorithms Alleles alpha 1-Antitrypsin - blood alpha 1-Antitrypsin - genetics alpha 1-Antitrypsin Deficiency - blood alpha 1-Antitrypsin Deficiency - complications alpha 1-Antitrypsin Deficiency - diagnosis alpha 1-Antitrypsin Deficiency - genetics Cross-Sectional Studies Female Genetic Predisposition to Disease Genetic Testing - methods Heterozygote Humans Immunoassay Isoelectric Focusing Male Middle Aged Nephelometry and Turbidimetry Original Papers Polymerase Chain Reaction Pulmonary Disease, Chronic Obstructive - blood Pulmonary Disease, Chronic Obstructive - diagnosis Pulmonary Disease, Chronic Obstructive - etiology Pulmonary Disease, Chronic Obstructive - genetics Sequence Analysis, DNA |
| Title | Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach? |
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