Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome

• Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 × 10−9. The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

LANTBRUKSVETENSKAPER  -- Veterinärmedicin (hsv//swe)

AGRICULTURAL SCIENCES  -- Veterinary Science (hsv//eng)

LANTBRUKSVETENSKAPER  -- Husdjursvetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Animal and Dairy Sience (hsv//eng)

Nyckelord

primary Sjögren's syndrome

IRF5

STAT4

single nucleotide polymorphisms

insertion–deletion polymorphism

MEDICINE

MEDICIN

Medicin

Medicine

insertion-deletion polymorphism

IRF5

primary Sjogren's syndrome

single nucleotide

STAT4

polymorphisms

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)