Table 2.
Genetics of cytokine network and viral pneumonia pathogenesis.
| Gene | Genetic background | Pneumonia and comorbidity states / prognosis (+/-) |
|---|---|---|
| Cytokines and their receptors | ||
| IL1A | A114S (rs17561) | H1N1 influenza A pneumonia predisposition / - [132] |
| Cancer (lung, ovarian, breast) predisposition / - [133,134,135]; Asthma prevalence / - [136] | ||
| IL1B | rs1143627 | Influenza A pneumonia / - [137] |
| rs16944 (511*C/T) | Cancer (lung, cervical) / + [138,139]; Autoimmunity / - [140] | |
| Systemic inflammatory response syndrome / - [141] | ||
| Diabetes / + [142]; Asthma / - [143] | ||
| IL1R1 | rs3917254; rs2160227 | Invasive pneumococcal disease / - [144,145] |
| IL1RA (secreted inhibitor for IL1) | A1A1 genotype | Community-acquired pneumonia / + [146] |
| A2A2 genotype | Asthma / - [147]; Diabetes / - [148] | |
| Community-acquired pneumonia / - [146] | ||
| Sepsis / - [149] | ||
| IL4 | C−590 T (rs 2,243,250) | Respiratory syncytial virus / - [150] |
| rs2070874 | Respiratory infection predisposition / - [151] | |
| Asthma / - [152]; Autoimmunity (rheumatoid arthritis) / - [153]; Cancer / - [154] | ||
| IL4RA | Q551R (rs1801275) | Respiratory syncytial virus / - [151] Asthma / - [155] |
| IL6 | GG genotype, G allele of IL6−174 G/C SNP (rs1800795) | Community-acquired pneumonia / - [156] |
| Immunodeficiency / - [157] | ||
| Pneumonia-induced sepsis /- [158] | ||
| Sepsis / + [159]; Cancer (various) / - [160]; Asthma / + [161] PMCID: PMC4612856 | ||
| IL9 | rs2069885 | Respiratory syncytial virus / - [162] Asthma / - [163]; COPD / - [164]; Lung inflammation (cystic fibrosis) / - [165] |
| IL10 | rs1800896-A | Community-acquired pneumonia / + [156] |
| rs1800871 (−819 T/T genotype) | Diabetes / - [166,167]; Asthma / - [168]; Breast cancer /- [169] | |
| Postoperative pneumonia / - [170] | ||
| IL12B | rs2195940, rs919766 | Invasive pneumococcal disease / - [145] Acute chest syndrome / - [171]; Inflammatory cardiomyopathy / - [172] |
| CCL5 | rs2107538*CT | Respiratory syncytial virus / - [173] |
| Cancer (breast, prostate) / - [174,175] | ||
| CCL2 | rs1024611 (G-2518A) | SARS-CoV / - [176] |
| Autoimmunity (multiple sclerosis) / - [177]; Cancer / - [178,179] | ||
| CCR5 | CCR5-Δ32 allele | Influenza A / - [180] |
| Diabetes / - [181,182]; Breast cancer / - [183,184] | ||
| TNFα | rs361525 | Influenza A / - [185] |
| 308*G/A (rs1800629) | Systemic inflammatory response syndrome / - [185]; Pneumonia-induced sepsis /- [158] | |
| −238A allele (rs361525) | Diabetic nephropathy / - [185,186]; Pneumonia in patients with systemic lupus erythematosus / - [187] | |
| TNFRSF1B | TNFRSF1B + 676 (rs1061622) | Community-acquired pneumonia / + [188] |
| Autoimmunity (systemic lupus erythematosus, rheumatoid arthritis) / - [189,190] | ||
| Lung cancer / + [191] | ||
| MIF | C allele at −173 G/C (rs 755,622); rs5844572 | Pneumonia-induced sepsis / + [89] |
| Meningitis and bacterial pneumonia / - [192] | ||
| Autoimmunity (systemic lupus erythematosus, rheumatoid arthritis) / + [193,194] | ||
| Transcription factors | ||
| NFκB cREL | rs842647*G | sepsis / - [195,196] |
| NFκB RelA (p65) | −94delATTG (rs28362491) | autoimmune (Behcet’s Disease) / - [197] |
| acute respiratory distress syndrome / - [198] | ||
| cancer / - or + [199,200]; diabetes / - [201] | ||
| STAT1 | L706S, Q463H, E320Q, P293L Complete Stat-1 deficiency |
mycobacterial disease / - [202,203] pneumonia / - [204] autoimmunity / - [204]; viral infections / - [205,206] |
| IRF5 | rs77571059, rs2004640, haplotype GTAA | community-acquired pneumonia / - |
| rs77571059 | autoimmunity (systemic lupus erythematosus, systemic sclerosis) / - [207,208,209,210,211] | |
| diabetes / - [212]; melanoma / - [213] | ||
| IRF7 | F410 V (rs 786,205,223) | influenza A / - [214] |
| rs375323253; Q421X | ||
| IRF9 | Loss-of-function IRF9 allele | Influenza A, parainfluenza virus, respiratory syncytial virus / - [215] |
| loss-of-function c.991 G > A | Influenza A, respiratory syncytial virus / - [216] | |