TABLE 3.
SINGLE-NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME IN STAGE II
| Gene | SNP | HWE P Value | ARDS MAF | No ARDS MAF | OR (95% CI) | P Value |
|---|---|---|---|---|---|---|
| Stage II genotyped SNPs |
|
|
|
|
|
|
| CHIT1 |
rs2494283T |
0.87 |
0.13 |
0.13 |
1.06 (0.73–1.55) |
0.77 |
| IL1RN |
rs315952C |
0.54 |
0.27 |
0.36 |
0.67 (0.52–0.88) |
0.0023 |
| CBS |
rs2124458C |
0.58 |
0.36 |
0.36 |
1.01 (0.78–1.31) |
0.92 |
| GPR98 |
rs17624740C |
1.0 |
0.08 |
0.07 |
0.95 (0.61–1.51) |
0.81 |
| ADA |
rs379863C |
0.37 |
0.21 |
0.19 |
1.11 (0.81–1.52) |
0.51 |
| Stage II imputed SNPs |
|
|
|
|
|
|
| TGFB2 |
rs10779329C |
|
0.24 |
0.25 |
0.99 (0.70–1.41) |
0.97 |
| IL1RN |
rs380092T |
|
0.29 |
0.36 |
0.71 (0.52–0.96) |
0.026 |
| UGT2B7 |
rs28365063G |
|
0.15 |
0.16 |
0.98 (0.67–1.43) |
0.92 |
| FZD2 |
rs8072266C |
|
0.04 |
0.03 |
1.49 (0.70–3.15) |
0.30 |
| VLDLR |
rs7865617T |
|
0.23 |
0.25 |
0.93 (0.68–1.27) |
0.64 |
| VLDLR |
rs6145T |
|
0.22 |
0.24 |
0.88 (0.64–1.22) |
0.44 |
| EPAS1 | rs7571879T | 0.06 | 0.09 | 0.75 (0.45–1.23) | 0.25 |
Definition of abbreviations: ARDS = acute respiratory distress syndrome; CI = confidence interval; HWE = Hardy-Weinberg equilibrium; MAF = minor allele frequency; OR = odds ratio; SNP = single-nucleotide polymorphism.
The SNPs meeting the stage I threshold for significance were tested in the stage II population (Harborview trauma), genotyped with the human 610-quad platform. SNPs are listed depending on whether their association with ARDS was determined by direct genotyping or by imputation using European haplotypes in 1000 Genomes (32). The α level to declare significance in stage II was 0.05/12 SNPs, or ≤0.0042. Only one SNP met this threshold: rs315952 (bold text) in IL1RN. By imputation, rs380092, also in IL1RN and with strong linkage disequilibrium with rs315952 (r2 = 0.73), showed a marginal ARDS association that did not survive adjustment for multiple comparison testing. HWE P values are the result of the chi-square statistic testing HWE proportions for the entire stage II population.