TABLE 2.
NON-HLA CANDIDATE GENE ASSOCIATIONS WITH SARCOIDOSIS
| Candidate Gene | Location | Association*† | Comment | References |
|---|---|---|---|---|
| Angiotensin-converting enzyme | 17q23 | C | Increased risk for ID and DD genotypes | 23, 24, 132–134 |
| Moderate association between II genotype and radiographic progression | ||||
| C-C chemokine receptor 2 | 3p21.3 | C+/− | Protection/LS association | 6, 29–31 |
| C-C chemokine receptor 5 | 3p21.3 | C− | Association of CCR5Delta32 allele more common in patients needing corticosteroid therapy. Refuted with haplotype analysis and larger sample. | 31, 35 |
| CD80, CD86 | 3q21 | No association detected | 43 | |
| Clara cell 10 kD protein | 11q 12-13 | C | A allele associated with sarcoidosis and with progressive disease at 3 yr follow-up. | 40 |
| Complement receptor 1 | 1q32 | A | The GG genotype for the Pro1827Arg(C(5,507)G) polymorphism was significantly associated with sarcoidosis. | 48 |
| Cystic fibrosis transmembrane regulator | 7q31.2 | A+/− | R75Q increases risk. | 51, 53 |
| HSPA1L heat shock protein 70 1 like (alias heat shock protein 70-hom) | 6p21.3 | C | HSP(+2437)CC associated with susceptibility and LS | 60 |
| Inhibitor κB-α | 14q13 | C | Association with −297T allele. Association of haplotype GTT at −881, −826, and −297, respectively. Allele −827T in Stage II. | 65 |
| IL-1α | 2q14 | A | The IL-1α −889 1.1 genotype increased risk. | 68 |
| IL-4 receptor | 16p11.2 | No association detected in 241 members of 62 families | 70 | |
| IL-18 | 11q22 | A+/− | Genotype −607CA increased risk over AA. No association with organ involvement. | 72–75 |
| IFN-γ | 9p22 | A | IFNA17 polymorphism (551T→G) and IFNA10 [60A] IFN-α17 [551G] haplotype increased risk. | 77 |
| Natural resistance associated macrophage protein | 2q35 | A | Protective effect of (CA)(n) repeat in the immediate 5′ region of the NRAMP1 gene | 81 |
| Toll-like receptor 4 | 9q32 | B | Asp299Gly and Thre399Ile mutations associated with chronic disease | 87 |
| TGF | 19q13.2 | B | TGF-β2 59941 allele, TGF-β3 4875 A and 17369 C alleles were associated with chest X-ray detection of fibrosis. | 85 |
| TNF-α | 6p21.3 | C+/− | Genotype −307A allele associated with Lofgren's syndrome and erythema nodosum and −857T allele with sarcoidosis. −307A not associated in African Americans. | 23, 92–95 |
| VEGF | 6p12 | C | Protective effect of +813 CT and TT genotypes | 135 |
| Vitamin D receptor | 12q12-14 | A− | BsmI allele elevated in sarcoidosis patients | 23, 106, 107 |
Definition of abbreviations: IL = interleukin; LF = Löfgren's syndrome; TNF = tumor necrosis factor; VEGF = vascular endothelial growth factor.
*
Type of association: A = susceptibility; B = disease course; C = both.
†
− = Association refuted; + = association replicated.