Table 1 Genetic associations involving molecules of the type I interferon pathway

1q21-24

FCGR2A

rs1801274 (R131H)

SLE, PAPS

R131 has lower affinity to IgG₂, which may affect the clearance of immune complexes

2q24.3

IFIH1 (MDA-5)

rs1990760 (T946A),

T1D, RA,

rs3747517 (R843H)

MS, GD

rs35337543 (G>C),

T1D

E627X and I923V are loss of function mutations.

rs35667974 (I923V),

E627X results in deletion of the C-terminal region necessary for dsRNA binding activity. I923V alters a conserved residue, which might impair the signaling

rs35744605 (E627X),

rs35732034 (G>A)

7q32

IRF5

CGGGG promoter insertion/deletion, rs2004640, exon 6 insertion/deletion rs10954213

RA, T1D, SLE, IBD, pSS

CGGGG and rs10954213 risk alleles enhance expression levels of IRF5. SNP rs2004640 and exon 6 insertion/deletion determine alternative splice isoforms

2q32.2

STAT4

rs7574865, rs7568275, rs3821236, rs10168266

RA, SLE, pSS, psoriasis, PAPS

Risk haplotype associated with high levels of expression and greater sensitivity to IFNα

9p13.2

TYK2

rs2304256, rs12720270, rs34536443

SLE, MS

rs12720270 located in a intron/exon boundary might be involved in alternative splicing

8p23-p22

BLK

rs13277113, rs2736340

SLE, PAPS

Promoter SNPs associated with reduced expression of BLK

4q24

BANK1

rs10516487 (R61H), rs17266594, rs3733197 (A383T)

SLE, RA

rs17266594 determines the transcription ratio between the full-length and delta 2 isoforms

Good evidence

1q21-24

FCGR3B

NA1/NA2, CNV of the whole gene

SLE, mPA, WG

NA1-homozygous has stronger FcγR-mediated phagocytic response. Increased risk for SLE with <2 gene copies

4q21-q25

SPP1

rs1126616, rs1126772, rs9138, rs7687316

3'-UTR polymorphisms associated with high amounts of ostepontin and IFNα in sera of patients with SLE. Evidence of rs9138-gender interaction

5q32-q33.1

TNIP1

rs10036748, rs7708392

SLE

No functional polymorphism yet identified. TNIP1 is the A20-binding inhibitor of NF-κB activation and together with A-20 serves as brake for interferon production induced via TLR

rs17728338

Psoriasis

16p13.3

DNASEI

V89M, K5X, 46_72 deletion, rs179982-rs1030874-rs1059857 haplotype,.

SLE, AITD

V89M and K5X are associated with lower enzymatic activity. Haplotype rs179982-rs1030874-rs1059857 defines isoforms of DNaseI

3p21.31

TREX1 (DNASEIII)

R114H, 158V, P212fs, G227S, R240S, A247, P272fs, P290L, Y305C, G306A

SLE, pSS

R114H associated with decreased exonuclease activity. Frameshift mutations D272fs and P212fs alter subcellular localization of the protein

Good evidence but more replication studies are required

2p13-p12

REL

rs13031237, rs13017599

RA

3q13.11

CBLB

F328L

T1D

1q21-24

FCGR3A

rs396991, V176F

Lupus nephritis

1q21-24

FCGR2B

I232T

SLE

8q13

LYN

rs6983130

SLE

5q31.1

IRF1

rs2070721

MS, JIA

2q.36

IRS1

rs1801278, G972R

T1D

16q24.1

IRF8

rs17445836

MS

2q32.2

STAT1

rs2066802, rs1547550

MS

11q24.2

TIRAP

rs8177374, S180L

SLE, IBD

Good evidence but more replication studies are required

6q21

ATG5

rs6568431

SLE

Xq28

IRAK1

rs2239673-rs763737-rs5945174-rs7061789 GGGG haplotype

SLE

Inconsistent replication

9q32-q33

TLR4

rs4986790 (G299D)

RA, GCA

9p22

IFNA gene cluster

SLE, MS

21q22.11

IFNAR cluster

IFNAR1:18417, IFNAR2: 11876

MS

4q24

NFKB1

-94 ATTG insertion/deletion, CA microsatellite

T1D, UC, GD

3p21.3

TLR9

+1174 A>G

SLE

17q21

STAT3

rs744166, rs12948909

CD

19q13.3-q13.4

IRF3

rs2304204, rs2304206

SLE