Gene ontology | Gene symbol | Polymorphism | Association with disease susceptibility | Pop. (cases/controls n) | [Refs] | |
Pro-/anti-inflammation | ||||||
IL-1 cluster | IL1A | −889C>T | No | CZ W (54/199) | 29+ | |
IL1B | −511C>T | No | CZ W (54/199) | 29 | ||
+3953C>T | No | CZ W (54/199) | 29 | |||
IL1RN | +2018C>T# | +2018T (OR 3.8) | UK W (88/88); IT W (61/103) | 30 | ||
Intron 2 VNTR# | No | CZ W (54/199); AU W (22/140) | 29, 31 | |||
TNF and related genes | TNF | −238G>A | No | UK W (74/201) | 32 | |
−308G>A | −308A (OR 13.9) | UK W-1 (88/88); IT (61/103); AU W (22/140) | 30, 31§ | |||
+488G>A | No | UK W (74/192) | 32 | |||
TNFRII | +676T>G | No | UK W (74/192) | 32 | ||
+1663G>A | No | UK W (74/192) | 32 | |||
+1668T>G | No | UK W (74/192) | 32 | |||
+1690T>C | No | UK W (74/192) | 32f | |||
LTA | +249A>G | No | UK W (74/201) | 32 | ||
+365C>G | No | UK W (74/201) | 32 | |||
+720C>A | No | UK W (74/201) | 32 | |||
IL6 | −174G>C | No | UK W (74/201); AU W (22/140) | 31, 32 | ||
Intron 4A>G | No | UK W (74/201) | 32## | |||
IL10 | +43G>A (G15R) | No | UK W (96/96) | 33 | ||
Chemokine-related genes | IL8 | −353A>T | No | UK W (71/194) | 34 | |
+293G>T | No | UK W (71/194) | 34 | |||
+678T>C | No | UK W (71/194) | 34 | |||
CXCR1 | +2607G>C | No | UK W (71/194) | 34 | ||
CXCR2 | +785C>T | No | UK W (71/194) | 34 | ||
+1208T>C | No | UK W (71/194) | 34 | |||
+1440G>A | No | UK W (71/194) | 34 | |||
Th1/Th2 response genes | IL12B | 3'UTR 1188A>C | No | UK W (73/157) | 35 | |
IFNG | 3'UTR 5644A>G | No | UK W (73/157) | 35 | ||
Complement receptor genes | CR1 | +3650A>G | No | IT W (74/166) | 36 | |
Intron 27 520T>C | No | IT W (74/166) | 36 | |||
+5507C>G (P1827R) | +5507G (OR 6.2) | IT W (74/166) | 36 | |||
Pulmonary surfactant | ||||||
Surfactant protein genes | SFTPA1 | 6A, 6A2, 6A3, 6A4¶ | 6A4 in NS only (OR 3.7) | MX (84/194) | 37 | |
SFTPA2 | 1A, 1A0, 1A1, 1A2, 1A5¶ | No | MX (84/194) | 37 | ||
SFTPB | 1580T>C (I131T) | 1580C in Sm only (OR 7.6) | MX (84/194) | |||
SFTPC | 438C>A (N138T) | No | MX (84/194) | 37 | ||
582G>A (N186S) | No | MX (84/194) | 37 | |||
SFTPD | ATG>ACG (M11T) | No | MX (84/194) | 37 | ||
ACA>GCA (T160A) | No | MX (84/194) | 37 | |||
Coagulation cascade | ||||||
PAI genes | PAI1 | Promoter region 4G/5G | No | USA W (62/2120) | 38 | |
Fibroblast-related pathways | ||||||
TGF-β genes | TGFB1 | +869T>C (L10P) | No | ES W (128/140) | 39¶¶ | |
+915G>C (R25P) | No | ES W (128/140); AU W (22/140) | 31, 39 | |||
RAAS-related genes | ACE | I/D | D | USA W (24/6000) | 40++ |
Pop.: population; IL: interleukin; TNF: tumour necrosis factor; Th: T-helper cell; PAI: plasminogen activator inhibitor; TGF: transforming growth factor; RAAS: renin–angiotensin–aldosterone system; IL1RN: IL-1 receptor antagonist gene; TNFRII: TNF receptor II gene; LTA: lymphotoxin-α gene; CXCR: CXC chemokine receptor gene; IFNG: interferon-γ gene; CR: complement receptor; SFTP: surfactant protein gene; TGFB1: TGF-β1 gene; ACE: angiotensin-converting enzyme; C: cytosine; T (nucleotide); thymidine; G (nucleotide): guanine; A (nucleotide): adenine; >: substitution; VNTR: variable number of tandem repeats; G15R; arginine I substituted for glycine (G (amino acid)) 15; P: proline; I: isoleucine; T (amino acid): threonine; N: asparagines; S: serine; M: methionine; A (amino acid): alanine; L: leucine; UTR: untranslated region; I/D: insertion/deletion; OR: odds ratio (maximum reported in homozygous subjects); NS: nonsmokers; Sm: smokers; AU: Australia; CZ: Czech Republic; ES: Spain; IT: Italy; MX: Mexico; W: White. #: in strong linkage disequilibrium; ¶: allelic variants; +: association between -889T and lower carbon monoxide diffusing capacity of the lung (DL,CO) 28; §: no association in UK W-2 32; f: co-carriage of C-allele and IL6 intron 4G; ##: association between IL6 intron 4GG genotype and lower DL,CO; ¶¶: association between +869C (10P) and deterioration in gas exchange; ++: small and heterogeneous study cohort.