Horizons in Sjögren’s Syndrome Genetics

Abstract

Sjögren's syndrome (SS) is a complex polygenic autoimmune disorder. A few major genetic effects have been identified. Historically, HLA and non-HLA genetic associations have been reported. Recently, the HLA region continued to reveal association findings. A new susceptibility region has been suggested by a study of a D6S349 microsatellite marker. Among non-HLA studies, recent association of immunoglobulin κ chain allotype KM1 with anti-La autoantibodies in primary Sjögren's syndrome confirms findings in a study from two decades ago. Meanwhile, mouse models have been employed to study the genetic contribution to salivary lymphadenitis or © Humana Press Inc. 2007 Correspondence to: John B. Harley, john-harley@omrf.ouhsc.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript dry eyes and mouth. Gene transfer exploration in mouse models shows promise. The authors review the HLA and non-HLA association studies and the mouse model work that has been reported. Newly developed genomic capacity will provide, in the future, a much closer approximation of the true picture of the genetic architecture of Sjögren's syndrome.

The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats

“…In the second week after stroke, the expression of Gpx1 and Ucp2 genes remained at high levels. In addition, the antioxidative capacity was further increased by up-regulation of gluthathione peroxidase 1, CAT and Sssca1 (a gene coding for Sjogren's syndrome/scleroderma autoantigen) [ 24 ].…”

“…In the second week after stroke, the antioxidative capacity of young rats was further improved by up-regulation of CAT, which has been intensively studied as an antioxidant in Sjogren's syndrome/scleroderma pathology. The expression of Sssca1 gene may reflect the generation of faulty proteins by oxidation [ 24 ].…”

Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome

“…5 Associations between primary SS and genes outside the HLA region have been investigated, but these studies were often performed in small cohorts with conflicting results or lack of replication, for a review, see reference. 6 These early studies detected associations with single-nucleotide polymorphisms (SNPs) in the interleukin 10 (IL10) promoter, Fas/FasL and with SNPs in the TGFb1 and TNFa genes in primary SS patients with anti-SSB antibodies.…”

Potential association of muscarinic receptor 3 gene variants with primary Sjogren's syndrome

“…In contrast to other genes reported to be associated with pSS, like STAT4 and IRF5, 6 8 9–13 CHRM3 has not been reported to be associated with other autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. Our observations therefore suggest that CHRM3 is a unique risk gene for pSS and the functional consequences of the identified SNPs need to be further elucidated.…”