Pulmonary Vascular Disease: Cystic Fibrosis |

Genotypes, Prevalence and Serum Levels of Alpha-1 Antitrypsin F and I Variants in a Clinical Screening Program FREE TO VIEW

Christopher Sanders, MS; Joannah Kim, MS
Author and Funding Information

Biocerna LLC, Gaithersburg, MD

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):1131A. doi:10.1016/j.chest.2016.08.1241
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SESSION TITLE: Cystic Fibrosis

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM

PURPOSE: To assess the prevalence and alpha-1 antitrypsin (AAT) serum levels associated with the rare F and I SERPINA1 variants in a large alpha-1 antitrypsin deficiency (AATD) screening program.

METHODS: Data was generated in the DNA1 Advanced Alpha-1 Screening™ Program (Biocerna, Gaithersburg, MD; funded by CSL Behring), which screens samples sent by physicians who suspect AATD in their patients. Blood samples collected on serum separator cards undergo a predetermined reflex testing strategy: A1-PI serum level by immunoturbidimetry (normal range 90-200 mg/dL), CRP level (≥5 mg/L indicative of inflammation), targeted genotyping, and reflex to isoelectric focusing for confirmation of abnormal variants. We report the frequency of F and I detection and associated AAT serum levels.

RESULTS: Among a total of 18,783 patients screened, 136 (0.72%) had at least one F allele. Of 14,735 patients screened for the I allele, 24 (0.16%) had at least one I allele. One patient had both alleles (PI*FI). The majority of the total F and I population (n=159) were PI*MF heterozygotes (n=123), followed by PI*MI (n=21) and PI*ZF (n=12), and the overall mean (SD) serum AAT level was normal at 141.2 (34.1) mg/dL. However, 13/159 patients (8.2%; mostly PI*ZF) had AAT <90 mg/dL. Mean serum AAT for PI*ZF was 75.0 (10.4) mg/dL. A further 11 patients (mostly PI*MF) had low-normal AAT between 90-110 mg/dL. Prevalence of F and I alleles in large populations has been reported at 0.40% and 0.21%, respectively.

CONCLUSIONS: A significant prevalence of I and F SERPINA1 variants was observed in the screened population, mostly comprising PI*MF heterozygotes. Most patients with I or F alleles exhibited normal AAT levels, but low levels were evident in combination with the Z allele. The frequency of F in our population was nearly twice as high as reported in population-based samples. Prevalence of I was similar to previous reports.

CLINICAL IMPLICATIONS: Normal AAT levels associated with the F and I variants may belie their true pathogenecity. Prevalence of the F allele in an enriched cohort of patients suspected to have AATD was nearly twice as high as in other large population-based samples. Further characterization of these variants is needed to understand their functional activity and potential clinical impact. Comprehensive AATD testing with the DNA1 kit can detect rare variants, avoid missed diagnoses and enable appropriate treatment.

DISCLOSURE: Christopher Sanders: Other: Biocerna performs the testing for CSL Behring's A1AT testing program. I am the Founder and CEO of Biocerna. Joannah Kim: Other: Biocerna performs the testing for CSL Behring's A1AT testing program.

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