Table 1.
Genetic studies in GCA focused on genes encoding MHC class II and various inflammatory molecules.
| Genes and No. of SNPs Tested |
GCA Patients/ Controls |
Associated SNP/Haplotype/ Variant with GCA * |
Method | Ref, Year |
|---|---|---|---|---|
| HLA DRB1 alleles | 20/242 | - | MLCA | [33], 1991 |
| HLA DRB1 alleles | 41/384 | HLA DRB1*04 (<0.001) | PCR | [31], 1998 |
| HLA DRB1 alleles | 42/63 | HLA DRB1*0401 or B1*0404/8 (<0.03) | PCR | [34], 1992 |
| HLA DRB1 alleles | 65/200 | HLA DR4 (<0.05) | MLCA | [27], 1988 |
| HLA DRB1 alleles | 42/1609 | HLA DRB1*04 (0.0005) | PCR | [28], 1998 |
| HLA DRB1 alleles | 52/72 | HLA DRB1*04 (0.0001) | PCR | [35], 1994 |
| MBL, HLA DRB1 alleles | 65/193 | HLA DRB1*04 (0.01) | PCR | [29], 2002 |
| HLA DRB1 alleles | 53/145 | HLA DRB1* 0401 (<0.05) | PCR | [36], 1998 |
| HLA DRB1 alleles | 44/99 | HLA-DRB1* 0401 HLA (0.02) and -DRB1* 0404 (0.04) | PCR | [30], 2004 |
| CCR5: 1 SNP | 176/180 | - | PCR-RFLP | [45], 2013 |
| CD24: 1 SNP | 120/195 | rs3838646 (0.01) and rs8743 (0.001) | Real-Time PCR | [46], 2008 |
| CRH: 2 SNPs | 62/147 | - | PCR-RFLP | [47], 2002 |
| CRP: 4 SNPs | 125/234 | - | Real-Time PCR | [48], 2009 |
| eNOS: 3 SNPs | 57/117 | C/1/T (0.04) and C/1/G (0.02) haplotypes | PCR | [49], 2003 |
| eNOS gene: 2 SNPs | 91/133 | 894 G/T (0.003) | PCR-RFLP | [50], 2003 |
| FCGR2A, FCGR3A, FCGR3B and FCGR2B: biallelic polymorphisms |
85/132 | FCGR2A-FCGR3A 131R-158F haplotype (0.01) | SSCP Assay and Sanger Sequencing | [51], 2006 |
| ICAM-1: 2 SNPs | 121/228 | G/R 241 (0.00005) | PCR-RFLP | [38], 2000 |
| ICAM-1: 2 SNPs | 58/129 | - | PCR-RFLP | [39], 2001 |
| IFN-γ microsatellite | 50/129 | - | PCR | [52], 2004 |
| IFN-γ: 4 SNPs and IL-4: 5 SNPs | IFN-γ: SNP2 rs2227284 (0.0001) and IL-4 haplotype: T-T-C-A-C (0.02) | Real-Time PCR | [53], 2004 | |
| IL-6: 1 SNP in the promoter | 62/124 | −174 G/C (0.03) | PCR | [54], 2002 |
| IL-6: 1 SNP in the promoter | 126/112 | - | PCR | [55], 2005 |
| IL-10: 2 SNPs in the promoter | 140/200 | IL-10 promoter: −592 C/A (0.004) | PCR-RFLP | [56], 2006 |
| IL-10: 2 SNPs in the promoter | 103/226 | IL-10 promoter: −592 C/A (0.004) | Real-Time PCR | [57], 2007 |
| IL17A: 5 SNPs | 1266/3779 | rs2275913 (0.01) and rs7747909 (0.04) | Real-Time PCR | [58], 2014 |
| IL-18: 3 SNPs | 212/405 | rs360719 (0.003) and rs1946518 (0.02) | Real-Time PCR | [59], 2010 |
| IL2/21: 1 SNP | 272/791 | - | Real-Time PCR | [60], 2011 |
| IL23R: 1 SNP and IL12RB2: 1 SNP | 357/574 | IL12RB2: rs3790567 (0.039) | Real-Time PCR | [61], 2011 |
| IL33: 6 SNPs and IL1RL1: 3 SNPs | 1363/3908 | IL33 gene: rs7025417 (0.041) | Real-Time PCR | [62], 2014 |
| IRAK1: 1 SNP and MECP2: 1 SNP | 627/1520 (only females) |
- | Real-Time PCR | [63], 2014 |
| IRF-5: 1 SNP and 1 indel | 220/520 | - | Real-Time PCR and Sanger Sequencing | [64], 2010 |
| MCP-1: 1 SNP in the promoter | 79/99 | haplotypes C-C (0.03) and T-T (0.005) | Real-Time PCR | [65], 2005 |
| MICA-TM microsatellite polymorphism and HLA-B genotyping | 98/225 | MICA A5 (0.0005) and HLA-B*15 alleles (0.04) | PCR | [66], 2007 |
| MIF: 1 SNP in the promoter | 83/122 | - | Sanger Sequencing | [67], 2005 |
| MMP-9: 7 SNPs | 30/23 | SNP rs2250889 (0.0009) | PCR-RFLP | [37], 2008 |
| MPO: 1 SNP in the promoter | 156/235 | −463 G/A (0.0002) | PCR-RFLP | [68], 2008 |
| NFKB1: 1 SNP in the promoter | 96/204 | - | Real-Time PCR | [69], 2006 |
| NLRP1: 1 SNP | 685/2898 | rs8182352 (0.0026) | Real-Time PCR | [70], 2013 |
| PTPN22: 1 SNP | 99/229 | - | Real-Time PCR | [71], 2005 |
| PTPN22: 2 SNPs and CSK: 2 Variants | 911/8136 | PTPN22: rs2476601/R620W (0.00002) | Real-Time PCR | [72], 2013 |
| STAT4: 1 SNP | 212/678 | - | Real-Time PCR | [73], 2009 |
| TLR4: 1 SNP | 210/678 | SNP rs4986790 (0.01) | Real-Time PCR | [74], 2009 |
| TNF microsatellite markers a-d | 62/147 | TNFa2 allele (0.003) and TNFa10 allele (0.02) | Sanger Sequencing | [75], 2000 |
| TNF-α, IL-1A and IL-1B genes: 5 SNPs | 57/128 | - | PCR | [76], 2002 |
| TRAF1: 1 SNP and C5: 1 SNP | 220/410 | - | Real-Time PCR | [77], 2010 |
| VEGF: 3 SNPS in the promoter | 92/200 | I (0.025) and C634 (0.015) | PCR-RFLP | [78], 2003 |
| VEGF: 2 SNPs | 103/226 | - | Real-Time PCR | [79], 2005 |
| CCL2, CCR7, IL10, IL12A, IL1A, IL1B, IL1RN, IL6, IL8, IFNG, LTA, eNOS, TNF and VEGF: 130 SNPs | 82/166 | eNOS (rs2779251), VEGF (rs1885657, rs2010963, rs699946 and rs699947), IL1RN (rs17207494), IL-6 (rs7805828 and rs1546766) and CCL2 (rs1860190) SNPs (<0.05) | Illumina Bead Array System | [80], 2012 |
CCL2: C motif chemokine ligand 2; CCR5: C-C chemokine receptor 5 gene; CCR7: C-C chemokine receptor type 7; CD24: cluster of differentiation 24; CRH: corticotropin-releasing hormone; CRP: C-reactive protein; CSK: C-terminal Src kinase; eNOS: endothelial nitric oxide synthase; FCGR2A: Fc gamma receptor 2A; ICAM-1: intercellular adhesion molecule 1; IFN-γ: interferon gamma; IL: interleukin; IL1RL1: interleukin 1 receptor-like 1; IL12RB2: interleukin 12 receptor subunit beta 2; IL23R: interleukin 23 receptor; indel: insertion/deletion; IRAK1: interleukin-1 receptor-associated kinase 1; IRF-5: interferon regulatory factor 5; LTA: lymphotoxin-α; MBL gene: mannose-binding lectin gene; MCP-1: monocyte chemoattractant protein 1; MECP2: methyl CpG binding protein 2; MLCA: microlympocytotoxicity assay; MICA-TM: major histocompatibility complex class I chain-related gene A transmembrane; MIF: macrophage migration inhibitory factor; MMP-9: matrix metalloproteinase 9; MPO: myeloperoxidase; NLRP1: NACHT; LRR; FIIND; CARD domain and PYD domains-containing protein 1; PCR: polymerase chain reaction; PTPN22: protein tyrosine phosphatase non-receptor type 22; RFLP: restriction fragment length polymorphism; SNP: single-nucleotide polymorphism; SSCP: single-stranded conformational polymorphism; STAT4: signal transducer and activator of transcription 4; TLR4: toll-like receptor 4; TNF: tumor necrosis factor; TRAF1: tumor necrosis factor receptor-associated factor 1; VEGF: vascular endothelial growth factor. * p-values are in parentheses.