History
Definitions, techniques, and nomenclature
Immunological typing
DNA-based typing
Current nomenclature
Heritability of RA and subphenotypes
Susceptibility
HLA
Position 11 | Position 71 | Position 74 | Haplotype name | Classical HLA-DRB1 alleles | Haplotype frequency (%) | OR for RA susceptibility | OR for RA severity |
---|---|---|---|---|---|---|---|
Valine
|
Lysine
|
Alanine
|
VKA-haplotype
|
*04:01
|
11
|
4.4
|
1.8
|
Valine
|
Arginine
|
Alanine
|
VRA-haplotype
|
*04:08, *04:05, *04:04, *10:01
|
6
|
4.2
|
1.8
|
Leucine
|
Arginine
|
Alanine
|
LRA-haplotype
|
*01:02, *01:01
|
11
|
2.2
|
1.5
|
Proline | Arginine | Alanine | PRA-haplotype | *16:01 | 1 | 2.0 | – |
Valine | Arginine | Glutamic acid | VRE-haplotype | *04:03, *04:07 | 1 | 1.6 | – |
Aspartic acid | Arginine | Glutamic acid | DRE-haplotype | *09:01 | 1 | 1.6 | – |
Valine | Glutamic acid | Alanine | VEA-haplotype | *04:02 | 1 | 1.4 | – |
Serine | Lysine | Alanine | SKA-haplotype | *13:03 | 1 | 1.0 | – |
Proline
|
Alanine
|
Alanine
|
PAA-haplotype
|
*15:01, *15:02
|
14
|
1.0
|
1.0
|
Glycine
|
Arginine
|
Glycine
|
GRQ-haplotype
|
*07:01
|
13
|
0.9
|
1.0
|
Serine
|
Arginine
|
Alanine
|
SRA-haplotype
|
*11:01, *11:04, *12:01
|
10
|
0.9
|
1.1
|
Serine | Arginine | Glutamic acid | SRE-haplotype | *14:01 | 3 | 0.8 | – |
Leucine | Glutamic acid | Alanine | LEA-haplotype | *01:03 | 0.4 | 0.7 | – |
Serine | Arginine | Leucine | SRL-haplotype | *08:01, *08:04 | 3 | 0.7 | – |
Serine
|
Lysine
|
Arginine
|
SKR-haplotype
|
*03:01
|
13
|
0.6
|
0.9
|
Serine
|
Glutamic acid
|
Alanine
|
SEA-haplotype
|
*11:02, *11:03, *13:01, *13:02
|
11
|
0.6
|
0.7
|
Non-HLA
Variations across ethnicities
Insights into pathogenesis
Severity
Gene name | Reference | Comment |
---|---|---|
HLA-DRB1
| ||
TRAF1
| Not associated in [93] | |
FOXO3
| Not associated in [96] | |
C5orf30
| [97] | Mechanism of action of the SNP studied in [98] |
IL2RA
| ||
IL2RB
| [100] | |
SPAG16
| [82] | GWAS |
CD40
| [101] | |
TNFAIP3
| Not associated in [93] | |
TNF-α
| [104] | |
IL-4 receptor
| ||
IL-4
| [107] | Not associated in [105] |
DKK-1
| [108] | |
MMP-9
| [109] | |
ZFP36L1 / C14orf181
| [109] | |
Granzyme B
| [110] | |
CCR5
| [111] | |
FCRL3
| [112] | |
IL15
| [113] | Not associated in Japanese [114] |
PADI4
| [84] | |
LILRA3
| [115] | |
SPP-1
| [116] | ACPA-negative RA |
Osteoprotegerin
| [117] | |
HUNK / SCAF4
| [83] | GWAS in ACPA-negative RA |
PTGER4
| [118] | |
CRP
| [119] |