RT Journal Article
SR Electronic
T1 LATE-BREAKING ABSTRACT: Effects of rare <em>SERPINA1</em> variants on emphysema and airtrapping in SPIROMICS
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA1214
DO 10.1183/13993003.congress-2016.PA1214
VO 48
IS suppl 60
A1 Victor Ortega
A1 Xingnan Li
A1 Wanda O'Neal
A1 R. Graham Barr
A1 David Couper
A1 Meilan Han
A1 Richard Kanner
A1 Eric Kleerup
A1 Fernando Martinez
A1 Stephen Peters
A1 Stephen Rennard
A1 Prescott Woodruff
A1 Eric Hoffman
A1 Deborah Meyers
A1 Eugene Bleecker
YR 2016
UL http://erj.ersjournals.com/content/48/suppl_60/PA1214.abstract
AB Background: PI type Z heterozygotes (Glu366Lys in SERPINA1) with a prior smoking history have been shown to have greater CT scan-based emphysema compared to PI MM wild types (Sorheim CHEST 2010). There are no studies evaluating the regional effects of rare SERPINA1 variants on CT scan-based emphysema or airtrapping.Aims and Objectives: The effects of rare SERPINA1 variants on regional CT scan emphysema and airtrapping were evaluated in NHLBI SPIROMICS.Methods: 1,715 non-Hispanic Whites(NHW), 392 African Americans, and 98 Hispanics with ≥20 pack-year smoking were genotyped for 24 rare coding variants (allele frequency≤5%). Regression-based models of CT scan emphysema (%lung area≤-950 HFU) and airtrapping (%≤-856 HFU) were performed.Results: In NHW, PI Z was associated with bilateral emphysema (CC=7.8%, CT=12%, TT=24%, p =5.5x10-8) and airtrapping (CC=25%, CT=34%, TT=54%, p =7.1x10-9). PI Z heterozygotes (MZ, N=73), PI Z homozygotes (ZZ, N=9), and PI Z-containing compound heterozygotes (ZS/ZVR, N=7) had greater bilateral emphysema (No Z=7.8%, MZ=12%, ZS/ZVR=13%, ZZ=24%, p=2.0x10-7), and airtrapping (No Z=25%, MZ=33%, ZS/VR=49%, ZZ=54%, p=2.7x10-8) compared to NHW without PI Z (No Z, N=1,499). Lower lung zone emphysema (p=0.008-0.04) and airtrapping (p=0.005-0.02) was lower in No Z compared to MZ. Upper and lower zone disease was lower in No Z versus ZZ (emphysema upper zones p=0.001-0.002, lower zones pp=1.2x10-9-1.2x10-8; airtrapping upper zones p=2.5x10-5-0.0004, lower zones p=4.0x10-9-9.9x10-9). ZS/ZVR had more upper zone airtrapping versus ZZ (p=0.03-0.04).Conclusions: In NHW, PI Z-containing SERPINA1 genotypes have cumulative effects on emphysema and airtrapping in both the upper and lower lung zones.