Gene ontology | Gene symbol | Polymorphism | Association with lung fibrosis in SSc | Pop. (cases/controls n) | Comments/other associations | [Refs] |
MHC | ||||||
HLA genes | DRB1 | HLA typing | DR11; DRB1*1104 | UK (202/307); GR (98/130) | 84, 85 | |
DPB1 | HLA typing | DPB1*1301 | UK (202/307) | 84 | ||
TNF | TNF | −237G>A | No | UK W (214/354) | 88 | |
−307G>A | No | UK W (214/354) | 88 | |||
−857C>T | −857T | UK W (214/354) | −857T in LD with DR11 | 88 | ||
−863C>A | No | UK W (214/354) | −863A strongly associates with ACA+ | 88 | ||
−1031T>C | No | UK W (214/354) | −1031C associates with ACA+ | 88 | ||
Non-MHC | ||||||
Chemokine-related genes | IL8 | −353A>T | No | UK W (128/194) | 34 | |
+293G>T | No | UK W (128/194) | 34 | |||
+678T>C | No | UK W (128/194) | 34 | |||
CXCR1 | +2607G>C | No | UK W (128/194) | 34 | ||
CXCR2 | +785C>T | +785C | UK W (128/194) | Also associated with SSc without lung fibrosis | 34 | |
+1208T>C | +1208T | UK W (128/194) | Also associated with SSc without lung fibrosis | 34 | ||
+1440G>A | No | UK W (128/194) | 34 | |||
Cytokine genes | TGFB1 | −509C>T | −509T | JP (87/110) | Weak association | 89 |
+869T>C (L10P) | +869C (OR 2.0) | JP (87/110); UK (152/147) | Also associated with SSc without lung fibrosis in UK patients | 89, 90 | ||
+915G>C (R25P) | No | UK (152/147) | 90 | |||
ECM | FN1 | HaeIII RFLP | Genotype AB | UK (161/253) | 91 | |
MspI RFLP | No | UK (161/253) | Co-carriage of genotypes MspI CD and HaeIII AB showed two-fold increased risk of developing lung fibrosis | 91 | ||
HindIII RFLP | No | UK (161/253) | 91 | |||
TaqI RFLP | No | UK (161/253) | 91 | |||
SPARC | +998C>G | No | USA W (94/70); AA (33/28); MA (51/45) | 92 | ||
+1551C>G | No | USA W (94/70); AA (33/28); MA (51/45) | 92 | |||
+1922T>G | +1922T | USA W (94/70); AA (33/28); MA (51/45) | Weak association | 92 | ||
FBN1 | Hap-1– -12 | Hap-5 | JP (106/100) | Hap-5/-6 associated with SSc in JP and Choctaw pops | 93 |
Pop.: population; MHC: major histocompatibility complex; HLA: human leukocyte antigen; TNF: tumour necrosis factor; ECM: extracellular matrix; IL: interleukin; CXCR: CXC chemokine receptor gene; TGFB1: transforming growth factor-β1 gene; FN: fibronectin; FBN: fibrillin; SPARC: secreted protein acidic and rich in cysteine; G: guanine; A: adenine; C: cytosine; T; thymidine; >: substitution; L10P: proline (P) substituted for leucine (L) 10; R: arginine; RFLP: restriction fragment length polymorphism; HaeIII: Haemophilus aegyptius III; MspI: Moraxella spp. I; HindIII: Haemophilus influenzae Rd III; TaqI: Thermus aquaticus YTI I; Hap: haplotype; OR: odds ratio (maximum reported in homozygous subjects); GR: Greece; JP: Japan; W: White; AA: African American; MA: Mexican American; LD: linkage disequilibrium; ACA+: anticentromere antibody positivity.