Abstract
Background
Available screening procedures for the detection of α1-antitrypsin-deficient (AATD) mutations have suboptimal cost-effectiveness ratios. The aim in this study was to evaluate and compare the viability of a composite approach, primarily based on the α1-globulin fraction, in identifying AAT genetic analysis eligible patients against standard screening procedures, based on clinically compatible profiling and circulating AAT < 1 g/L.
Methods
A total of 21,094 subjects were screened for AATD and deemed eligible when meeting one of these criteria: α1-globulin ≤2.6%; α1-globulin 2.6%–2.9% and AST: >37 U/L and ALT: > 78 U/L; α1-globulin %: 2.9–4.6% and AST: >37 U/L and ALT: >78 U/L and erythrocyte sedimentation rate (ESR) >34 mm/h and C-reactive protein (CRP) >3 mg/L. Subjects were genotyped for the AAT gene mutation. Detection rates, including those of the rarest variants, were compared with results from standard clinical screenings. Siblings of mutated subjects were included in the study, and their results compared.
Results
Eighty-two subjects were identified. Among these, 51.2% were found to carry some Pi*M variant versus 15.9% who were clinically screened. The detection rates of the screening, including relatives, were: 50.5% for the proposed algorithm and 18.9% for the clinically-based screening. Pi*M variant prevalence in the screened population was in line with previous studies. Interestingly, 46% of subjects with Pi*M variants had an AAT plasma level above the 1 g/L threshold.
Conclusions
A composite algorithm primarily based on the α1-globulin fraction could effectively identify carriers of Pi*M gene mutation. This approach, not requiring clinical evaluation or AAT serum determination, seems suitable for clinical and epidemiological purposes.
Acknowledgments
Authors wish to acknowledge the technical and data management support received by Katia Monnati, Eng., and Alessandra Bollettieri, Eng., at Help Desk Medarchiver board; Marco Venditti, Eng., head of the IT Operations Unit at Campus Bio Medico University and Teaching Hospital.
Author contributions: SSc, SSan and RAI participated in the study concept and design; SSc, SSan, PF and DF collected the data; IF, SO and AGC were in charge of the blood sample genotyping; SSc and PF performed data analyses; SSc, SSan, PF, IF, AGC, MM and RAI reviewed the manuscript for important intellectual content. The authors fulfill authorship criteria, they revised the final version of the manuscript and consented to publication.
Research funding: None declared.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Local ethical board approval released on September 21st 2016, protocol number: 43/16 OSS ComEt CBM.
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