Genetics in neuroendocrine immunology: implications for rheumatoid arthritis and osteoarthritis.
Both genetic and environmental factors contribute to rheumatoid arthritis (RA) as well as osteoarthritis (OA). For RA, most of the known genetic markers are linked with genes from immunological pathways. Recent genome-wide association studies (GWAS) on RA identified known and novel susceptibility genes like HLA-DRB1, PTPN22, STAT4, TRAF1/C5, OLIG3/TNFAIP3, CD40, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, IL2RB, and KIF5A-PIP4K2C. These association signals explain more than 50% of the genetic influence on RA. In contrast, less GWAS data for OA exist. Most OA susceptibility genes arose from classical candidate gene analyses and were not replicated in all study samples. Neuroendocrine factors are hypothesized to play an important role both in RA and OA etiology. Here, we discuss these findings and present an outlook for genetic association studies after GWAS.
Stark
Klaus
K
Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
Straub
Rainer H
RH
Blazicková
Stanislava
S
Hengstenberg
Christian
C
Rovenský
Jozef
J
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009490:Neurosecretory Systems / Q000276:immunology*; D010003:Osteoarthritis / Q000235:genetics*; D011110:Polymorphism, Genetic
D005819:Genetic Markers