Ilaria Ferrarotti, Bi.Sci., PhD
New confidence intervals for AAT plasma levels by identification of SERPINA1 gene recurrent haplotypes
The only ascertained individual risk factor for COPD is plasma level of AAT, and the SERPINA1 genotypes dictate the serum AAT concentration in a co-dominant fashion. The risk for COPD is well defined for subjects displaying absent (PI*NullNull) or extremely low (PI*ZZ; ~15% of normal PI*MM) level of AAT. The risk decreases progressively according to the hierarchy
PI*SZ (AAT level ~40% of normal)
> PI*MZ (AAT level ~60% of normal)
> PI*MS (AAT level ~80% of normal)
> PI*MM. In a recent survey developed
within the core of the Italian screening program for AAT Deficiency (AATD), it was noticed that, besides the groups of AATD individuals carrying the PI*ZZ and PI*SZ genotypes, there was an unexpectedly large group of subjects carrying at least one rare AATD allele (called R). An increasing prevalence of COPD was detected according to the hierarchy PI*MZ (38%) and PI*SZ (38%) < M/R (46%) < PI*ZZ (79%) < R/D (100 %) (4). Accordingly, the magnitude of FEV1/FVC ratio impairment followed the same hierarchy: PI*MZ (0.74) < PI*SZ (0.71) < M/R (0.67) < PI*ZZ (0.57) < R/D (0.39). Since it is widely accepted that phenotypes result from the interaction between genetic determinants (in this case, the plasma levels of AAT), and environmental determinants (in this case, cigarette smoking), then the phenotypic ranking seem to result from the interaction between the AAT plasma levels reported in this series, with the R/D and PI*ZZ groups at the lowest end (29 and 28 mg/dl, respectively), followed by PI*SZ (62 mg/dl) and M/R (61 mg/dl), and with PI*MZ individuals at the highest end 93 mg/dl), and the smoking prevalence, ranking R/D (100%) > M/R (85%) >PI*ZZ (67%) > PI*SZ (52%) and PI*MZ (52%). These findings further support the concept that the genetic risk factor for COPD is significantly related to the AAT level and that cigarette smoking may influence the risk rate. In addition, although the terms of "severe AAT Deficiency" or "intermediate AAT Deficiency" are widely used, a clear-cut definition of plasma AAT level range identifying such categories is still lacking. ...
Curriculum Vitae of Ilaria Ferrarotti
|
Clinica di Malattie Apparato Respiratorio, Pavia, Italy |
|
| Current position: |
Contract researcher at "Laboratorio di Biochimica e Genetica delle Malattie Respiratorie" – Policlinico S. Matteo, Pavia, Italy |
|
Education: |
|
| 1999 |
Degree in Biology, University of Pavia |
| 2003 |
Postgraduation in Clinical Biochemistry, University of Pavia |
|
Professional experience: |
|
| 1999 - 2000 |
Fellowship at "HLA laboratory" – Policlinico S. Matteo, Pavia |
| 2000 - 2003 |
Fellowship at "Laboratorio di Biochimica e Genetica delle Malattie Respiratorie" – Policlinico S. Matteo, Pavia |
| 2003 - present |
Contract researcher at "Laboratorio di Biochimica e Genetica delle Malattie Respiratorie" – Policlinico S. Matteo, Pavia |
| 2005 - present |
Coordinator, "Centre for Diagnosis of Inherited Alpha-1-Antitrypsin Deficiency" – Policlinico San Matteo, Pavia |
|
Primary research interests: |
Genetic reseach on inflammatory lung disease. Diagnosis of AATD and related research: molecular characterization of rare variants, epidemiology, correlation among genotypes and clinical phenotypes. |
Contact
Ilaria Ferrarotti, Bi.Sci., Ph.D.
Clinica di Malattie Apparato Respiratorio
IRCCS Policlinico San Matteo
Via Taramelli 5
27100 Pavia
Italy
Telephone: +39 (0) 3 82 / 50 10 04
Fax: +39 (0) 3 82 / 50 22 69
E-mail: i.ferrarotti@smatteo.pv.it