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- W2555574708 abstract "Background: PI type Z heterozygotes (Glu 366 Lys 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/ZV R , N=7) had greater bilateral emphysema (No Z=7.8%, MZ=12%, ZS/ZV R =13%, ZZ=24%, p=2.0x10 -7 ), and airtrapping (No Z=25%, MZ=33%, ZS/V R =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/ZV R 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." @default.
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- W2555574708 date "2016-09-01" @default.
- W2555574708 modified "2023-10-02" @default.
- W2555574708 title "LATE-BREAKING ABSTRACT: Effects of rareSERPINA1variants on emphysema and airtrapping in SPIROMICS" @default.
- W2555574708 doi "https://doi.org/10.1183/13993003.congress-2016.pa1214" @default.
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