Background
Methods
Study subjects
Genotyping
Statistical analysis
Results
General characteristics
Variable | Fast decline (n = 275) | No decline (n = 304) | p Value* |
---|---|---|---|
Age, yr† | 49.5 (6.4) | 47.6 (6.9) | 0.0007 |
Sex, n (%) | 163 men (59) | 203 men (67) | 0.06 |
Smoking history, pk yrs†‡ | 43.3 (19.1) | 38.3 (18.1) | 0.0005 |
Baseline FEV1, % predicted†§ | 72.7 (8.9) | 75.7 (8.1) | <0.0001 |
Methacholine response†ll | -23.4 (32.7) | -7.5 (14.0) | <0.0001 |
DEFA1 and DEFA3 genes and rate of decline in lung function
DEFB1 gene polymorphisms and rate of decline in lung function
Polymorphism | Phenotype | Genotype | ||
---|---|---|---|---|
G-20A | GG | GA | AA | |
(rs11362) | Fast decline | 83 (30.2) | 131 (47.6) | 61 (22.2) |
No decline | 91 (29.9) | 150 (49.3) | 63 (20.7) | |
*p = 0.89 | ||||
C-44G | CC | CG | GG | |
(rs1800972) | Fast decline | 177 (64.4) | 85 (30.9) | 13 (4.7) |
No decline | 198 (65.1) | 91 (29.9) | 15 (4.9) | |
*p = 0.97 | ||||
G-52A | GG | GA | AA | |
(rs1799946) | Fast decline | 107 (38.9) | 128 (46.6) | 40 (14.6) |
No decline | 130 (42.8) | 128 (42.1) | 46 (15.1) | |
*p = 0.55 |
DEFB1 linkage disequilibrium and haplotype association analysis
D' (D/Dmax) | r2
| p Value* | |
---|---|---|---|
G-20A and G-52A | 0.75 | 0.29 | <0.00001 |
G-20A and C-44G | 0.88 | 0.17 | <0.00001 |
C-44G and G-52A | 0.93 | 0.13 | <0.00001 |
Imputed haplotypes (-20/-44/-52) | Fast decline, n (%) | No decline, n (%) | p Value* |
---|---|---|---|
ACA | 24 (4.4) | 18 (3.0) | 0.26 |
GCA | 181 (32.9) | 201 (33.1) | |
GGA | 3 (1.0) | 1 (<1.0) | |
ACG | 223 (40.6) | 257 (42.3) | |
GCG | 11 (2.0) | 11 (1.8) | |
AGG | 6 (1.1) | 1 (<1.0) | |
GGG | 102 (18.6) | 119 (19.6) |
Secondary outcomes analysis
Polymorphism | Genotype | Physician visits‡§ | Part 1 p Value* | Part 2 p Value† | Days in bed‡ll | Part 1 p Value* | Part 2 p Value† |
---|---|---|---|---|---|---|---|
DEFA1/DEFA3 | |||||||
DEFA1 only | 0.22 (0.07) | 0.23 | 0.05 | 0.38 (0.16) | 0.60 | 0.36 | |
DEFA1/DEFA3 | 0.28 (0.02) | 0.51 (0.06) | |||||
DEFB1 G-20A | |||||||
GG | 0.27 (0.04) | 0.85 | 0.88 | 0.49 (0.10) | 0.86 | 0.98 | |
GA | 0.26 (0.03) | 0.48 (0.08) | |||||
AA | 0.30 (0.05) | 0.54 (0.11) | |||||
DEFB1 C-44G | |||||||
CC | 0.28 (0.03) | 0.81 | 0.42 | 0.53 (0.07) | 0.93 | 0.14 | |
CG | 0.27 (0.04) | 0.44 (0.10) | |||||
GG | 0.18 (0.10) | 0.28 (0.24) | |||||
DEFB1 G-52A | |||||||
GG | 0.29 (0.04) | 0.67 | 0.62 | 0.47 (0.08) | 0.81 | 0.29 | |
GA | 0.25 (0.03) | 0.47 (0.08) | |||||
AA | 0.30 (0.06) | 0.62 (0.14) |
Haplotype | Physician visits‡§ | Part 1 p Value* | Part 2 p Value† | Days in bed‡ll | Part 1 p Value* | Part 2 p Value† |
---|---|---|---|---|---|---|
ACA | 0.26 (0.08) | 0.84 | 0.88 | 0.60 (0.19) | 0.40 | 0.10 |
GCA | 0.27 (0.03) | 0.50 (0.06) | ||||
GGA | 0.50 (0.27) | 2.50 (0.63) | ||||
ACG | 0.28 (0.02) | 0.50 (0.06) | ||||
GCG | 0.45 (0.11) | 1.00 (0.27) | ||||
AGG | 0.23 (0.20) | 0.60 (0.48) | ||||
GGG | 0.24 (0.04) | 0.36 (0.08) |
Alpha-defensin and beta-defensin polymorphisms in different racial groups
Polymorphism | Genotype | White (n = 579)† | African American (n = 27)† | p Value* |
---|---|---|---|---|
DEFA1/DEFA3 | ||||
DEFA1 only | 11.1 | 22.2 | 0.08 | |
DEFA1/DEFA3 | 88.9 | 77.8 | ||
DEFB1 G-20A | ||||
GG | 30.1 | 44.4 | 0.21 | |
GA | 48.5 | 44.5 | ||
AA | 21.4 | 11.1 | ||
DEFB1 C-44G | ||||
CC | 64.8 | 100.0 | 0.0008 | |
CG | 30.4 | 0.0 | ||
GG | 4.8 | 0.0 | ||
DEFB1 G-52A | ||||
GG | 40.9 | 22.2 | 0.001 | |
GA | 44.2 | 37.1 | ||
AA | 14.9 | 40.7 |