Table 1.
Previously reported T1D loci in extended MHC
| MHC region | Loci | Position (Mb) | References | Evidence for association | Subjects and methods of analyses |
|---|---|---|---|---|---|
| Class II | DPB1 | 33.16 | Cucca et al. (2001) | DPB1*0402 protective mainly on DR4-negative haplotypes (DPB1*0301 at 5.4-fold greater risk than DPB1*0402 on DR3 haplotypes) | Haplotype method transmission disequilibrium test (HM-TDT) adjusted for DR-DQ: 408 European families |
| Cruz et al. (2004) | DPB1*0301 (p = 0.002), DPB1*0202 (p = 0.027) predisposing; DPB1*0402 (p = 0.012) protective | TDT adjusted for DR-DQ: 84 Mexican-American families | |||
| Howson et al. (2009) | Overall p = 5.1 × 10−8 | Recursive partitioning (RP) and logistic regression (LR) controlled for DR-DQ: proband dataset of 2,300 families (T1DGC) | |||
| DOA | 33.08 | Santin et al. (2009) | SNP rs419434 (unconditional OR 1.93; CI 1.52–2.44; p = 10−8) | 15 DR3 homozygous cases and 39 controls with one copy of B18-DR3 extended haplotype for initial screening. 554 cases and 841 controls of southern European origin for Fisher’s exact test in replication study | |
| Class III | HLA-DRA | 32.52 | Nejentsev et al. (2007) | SNP rs9268831 (p = 6.95 × 10−8) | RP and LR controlled for DR-DQ: 2,484 cases and 2,019 controls, mainly Caucasian |
| Centromeric of NOTCH4 | 32.30 | Valdes et al. (2009) | SNP rs2395106 (p = 3.3 × 10−4) | Overall conditional genotype method (OCGM) controlled for DR-DQ: 886 Caucasian families | |
| CFB | 32.02 | Valdes et al. (2010) | SNP rs4151659 on DR3 (p = 1.2 × 10−9) and DR4 (p = 4 × 10-15) haplotypes | TDT on the DR3 and DQ4 haplotypes: 1,411 Caucasian families (T1DGC) | |
| MSH5 | 31.83 | Valdes et al. (2009) | SNP rs707915 (p = 3.5 × 10−4) | OCGM controlled for DR-DQ: 886 Caucasian families | |
| AIF1 | 31.69 | Eike et al. (2009b) | SNP rs2259571 (p = 0.034) | Logistic regression adjusted for DR-DQ: 434 Norwegian families | |
| TNF (200-kb region) | 31.65 | Hanifi Moghaddam et al. (1998) | Microsatellite D6S273 | 120 cases and 83 controls from Belgium matched for DQA1*0301-DQB1*0302 and DQA1*0501-DQB1*0201 | |
| 5’ of LTA | 31.65 | Valdes et al. (2010) | SNP rs7762619 on DR3 (p = 2 × 10−12) and DR4 (p = 8 × 10-8) haplotypes | TDT on the DR3 and DQ4 haplotypes: 1,411 Caucasian families (T1DGC) | |
| Class I | HLA-B | 31.43 | Nejentsev et al. (2000) | Microsatellites C12A (p = 0.00326), STR MICA (p = 0.00018), C125 (p = 0.00239) and C143 (p = 0.00013) for DR3/404; MIB (p = 0.00463) for DR3/401 | Population differentiation test: 75 cases and 181 controls for DR3/404 genotype, and 241 cases and 354 controls for DR3/401 genotype. All from Finland |
| Valdes et al. (2005) | B*4403 (p = 0.036) protective; B*1801 (p = 0.038), B*3906 (p = 0.002) predisposing | TDT adjusted for DR-DQ: 283 Caucasian multiplex families from US | |||
| Nejentsev et al. (2007) | Overall p = 2.01 × 10−19: B*39 predisposing | Recursive partitioning and logistic regression controlled for DR-DQ: 2,484 cases and 2,019 controls, mainly Caucasian | |||
| Eike et al. (2009a) | Overall p = 5.7 × 10−12: B*44 protective; B*39, B*18 predisposing | LR controlled for DR-DQ: proband dataset of 2,312 families (T1DGC) | |||
| Howson et al. (2009) | Overall p = 6.0 × 10−17: B*38 most protective (OR 0.51; CI 0.14–1.77); B*39 most predisposing (OR 2.53; CI 1.57–4.07) | RP and LR controlled for DR-DQ: proband dataset of 2,300 families (T1DGC) | |||
| HLA-C | 31.35 | Valdes et al. (2005) | C*0802 (p = 0.049), C*1601 (p = 0.049) protective; C*0303 (p = 0.0032) predisposing | TDT adjusted for DR-DQ: 283 Caucasian multiplex families from US | |
| HLA-A | 30.02 | Noble et al. (2002) | A*0101 (p = 0.007) protective; A*2402 (p = 0.026), A*3002 (p = 0.046) predisposing | TDT adjusted for DR-DQ: 283 Caucasian multiplex families from US with two affected siblings and unaffected parents | |
| Nejentsev et al. (2007) | Overall p = 2.35 × 10−13: A*01, A*11, A*31 protective; A*24 predisposing | RP and LR controlled for DR-DQ: 2,484 cases and 2,019 controls, mainly Caucasian. | |||
| Howson et al. (2009) | Overall p = 8.8 × 10−13: A*32 most protective; A*24 most predisposing | RP and LR controlled for DR-DQ: proband dataset of 2,300 families (T1DGC) | |||
| HLA-G | 29.91 | Eike et al. (2009a) | SNPs rs4122198 (p = 1.5 × 10−8), rs2394186 (p = 2.1 × 10−8), rs1619379 (p = 1.1 × 10−7) and rs1611133 (p = 3.2 × 10−6) | LR controlled for DR-DQ: 2,321 families (T1DGC) | |
| Between UBD and MAS1L | 29.63–29.56 | Aly et al. (2008) | SNP rs1233478 (p = 1.4 × 10−12 after chromosomes with the highly conserved MHC 8.1 haplotype were removed) | AFBAC: 237 families from US; 1,240 families from UK, US and Denmark (T1DGC) for replication | |
| Extended Class I | Telomeric of HLA-F | 27.77 | Lie et al. (1999) | Microsatellite D6S2223*3 (p = 0.00004) protective | Homozygous parent TDT (HPTDT) on DRB1*03-DQA1*0501-DQB1*0201: 116 families from Norway, Denmark and UK |
| Johansson et al. (2003) | D6S2223*3 (p = 0.03) protective | HPTDT on DRB1*03-DQA1*0501-DQB1*0301: 43 families from Sweden and Southern France | |||
| Santin et al. (2009) | D6S2223*3 (p = 0.001) protective | HPTDT on DRB1*03-DQA1*0501-DQB1*0201: 111 Caucasian parents | |||
| PRSS16 | 27.33 | Santin et al. (2009) | SNPs rs6931711, rs858988, rs9368492, rs9393796, rs9348756, rs9368493 and rs6938397 (p = 0.02, all SNPs in perfect LD) | HPTDT on DRB1*0401-DQA1*03-DQB1*0302: 62 Caucasian parents | |
| BTN3A2 | 26.48 | Viken et al. (2009) | SNP rs9379857 (p = 0.01) | HPTDT on DRB1*03-DQA1*0501-DQB1*0201: 111 Caucasian parents |