Details

Autor(en) / Beteiligte

• El-Gabalawy, H S
• Robinson, D B
• Daha, N A
• Oen, K G
• Smolik, I
• Elias, B
• Hart, D
• Bernstein, C N
• Sun, Y
• Lu, Y
• Houwing-Duistermaat, J J
• Siminovitch, K A

Titel

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population

Ist Teil von

• Genes and immunity, 2011-10, Vol.12 (7), p.568-574

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Most of the genetic risk for rheumatoid arthritis (RA) is conferred by 'shared epitope' (SE), encoding alleles of HLA-DRB1. Specific North American Native (NAN) populations have RA prevalence rates of 2-5%, representing some of the highest rates estimated worldwide. As many NAN populations also demonstrate a high background frequency of SE, we sought to determine whether other genetic factors contribute to disease risk in this predisposed population. RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL. Our findings indicate that SE is prevalent and represents a major genetic risk factor for RA in this population (82% cases versus 68% controls, odds ratio=2.2, 95% confidence interval 1.6-3.1, P<0.001). We also demonstrate that in the presence of SE, the minor allele of MMEL1-TNFRSF14 significantly reduces RA risk in a dominant manner, whereas TRAF1-C5 increases the risk. These findings point to the importance of non-HLA genes in determining RA risk in a population with a high frequency of disease predisposing HLA-DRB1 alleles.