Table 3.
Top Single Nucleotide Polymorphisms and Genes in Acute Respiratory Distress Syndrome Literature—Candidate Gene Risk
| Gene | Predictive SNPs | Population | Study |
|---|---|---|---|
| Candidate gene risk SNPs | |||
| ACE | D/D (p = 0.00004, healthy population, p = 0.0008 CABG patients) | European descent (University of College London Hospitals) | 88 Respiratory failure patients, 174 CABG controls (192) |
| AGER | Rs2070600 (A/A, Ser/Ser, p < 0.0001) | European descent (Clermont-Ferrand, France) | 59 ARDS, 405 controls; log rank test with case–control (178) |
| AGT | Rs699 (0.028, dom) | European descent (Moscow, Russia) | 68 NP ARDS cases, 198 NP controls (179) |
| AhR | Rs2066853 (0.0012, dom) | European descent (Moscow, Russia) | 68 NP ARDS cases, 198 NP controls (179) |
| CYP1A1 | Rs2606345 (0.0027, dom) | European descent (Moscow, Russia) | 68 NP ARDS cases, 198 NP controls (179) |
| DIO2 | Rs12885300 (p = 0.039) | African and European descent (American-European Consensus Criteria) | 327 European Americans: 139 sever sepsis, 78 severe sepsis + ARDS/ALI, 188 controls; 261 African Americans: 78 severe sepsis, 41 severe sepsis + ARDS/ALI, 187 controls (187) |
| Rs225014 (p = 0.009) | |||
| EGF | Rs4444903 (p = 0.005, males), rs2298991 (p = 0.019, males), Rs7692976 (p = 0.005, males), Rs6533485 (p = 0.025, males) | European descent (MGH, Boston, MA) | 416 ARDS cases (246 survivors, 170 died), 1052 ICU controls; 887 males and 581 females (180) |
| GADD45a | Rs581000 (p = 0.009) | African Americans Chicago Study and Spanish Study (Chicago, IL) | African American Chicago cohort: 71 severe sepsis, 40 sepsis + ALI, 182 controls; Spanishcohort: 80 severe sepsis, 66 sepsis + ALI, 95 controls (61) |
| IL-13 | 1 SNP (431 A>Gr, p = 0.008) | European descent (Moscow, Russia) | 347 Controls, 74 ARDS cases; logistic regression adjusted case/control (98) |
| IL-4 | 1 SNP (−589 C>T, p = 0.01) | European descent (Moscow, Russia) | 345 Controls, 72 ARDS cases; logistic regression adjusted case/control (98) |
| IL-6 | −174G/C allele (p = 0.03) | European descent | Twin study on lung function, 427 twins (232 women, 195 men) (36, 41) |
| MAP3K1 | Rs832582 (p = 0.01, rec) | FACTT and ARDSNet (Seattle WA) | 241 ARDS patients, 346 healthy, locally matched controls (193) |
| MIF | 2 SNPs (rs755622, p = 0.03; Rs2070767, p = 0.04) | European descent, African descent | 288 European: 113 severe sepsis, 90 sepsis-associate ALI, 85 healthy controls; 218 African: 69 severe sepsis, 61 sepsis-associated ALI, 88 healthy controls (50) |
| MYLK | Rs820336 (p = 0.002) | European and African descent (John Hopkins University and Medical College of Wisconsin) | European: 92 ALI, 99 sepsis, 85 healthy controls; African: 43 ALI, 51 sepsis, 61 healthy control (91) |
| Rs936170 (p = 0.009) | |||
| Rs936170 (p = 0.025) | |||
| NAMPT/PBEF | 2 SNPs (−948, p = 0.015–2422, p = 0.03) | European descent | 374 ARDS patients and 787 at-risk controls; nested case–control (88) |
| NFE2L2 | 7 SNPS (p-values: 0.0069–0.0089) | Spanish Network | 321 Severe sepsis and ARDS; 871 population-based controls; case–control (76) |
| PI3 | Rs1983649 (p = 0.034, add), Rs2664581 (p = 0.004, 0.023, add, dom) | European descent (MGH, Boston, MA) | 449 ARDS patients, 1031 at-risk controls; case–control (181, 182) |
| S1PR3 | 2 SNPS (rs7022797, p = 0.017; Rs11137480, p = 0.042) | European and African descent (Chicago, IL) | 71 European ARDS and 24 African ARDS; 186 European controls, 185 African controls (66) |
| SP-B | 1 SNP (606-bp variant allele, 1580 C/T) | MGH (Boston, MA), European descent (German) | 72 ARDS cases, 117 controls; nested case–control (177) 52 ARDS patients, 46 healthy controls (44) |
| TLR1 | 1 SNP (rs5743551, p = 0.002) | European descent (Seattle, WA) | 138 Severe sepsis ARDS, 107 ALI, 167 healthy controls (23) |
| Candidate gene survival-specific risk SNPs | |||
| IL-1B | 1 SNP (−511 G>A, p = 0.0019) | European descent (Moscow, Russia) | 321 Controls, 91 mortality cases; adjusted logistic regression for case–control mortality (150) |
| NAMPT/PBEF | −1001G (p = 0.001) | European descent | 374 ARDS patients and 787 at-risk controls; nested case–control (101) |
| −1543T (p = 0.03) | |||
| PHD2 | 1 SNP (rs516651, p = 0.002) | European descent (Duisburg-Essen, Germany) | 264 ARDS (70 died); case–control (184) |
| TNF | TNF-308 (p = 0.0006) | Brazilian septic and ARDS pediatric patients | 490 Septic and ARDS patients; 610 controls (119) |
| TNF-863 (p = 0.01) | |||
CABG, coronary artery bypass graft; D/D, deletion/deletion; DIO2, iodothyronine deiodinase 2; GADD45a, growth arrest and DNA damage-inducible gene; NP, nosocomial pneumonia.