Associations of Killer Cell Immunoglobulin-Like Receptor Genes with Rheumatoid Arthritis

Abstract

Objective: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28nullT-cells, both present in synovial membrane of RA. Therefore we evaluated the associations ofKIRgenes with RA.Methods: 16KIRgenes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences inKIRgenotypes and gene frequencies were assessed using theX2test.Results: Gene frequency ofKIR2DL3was lower in RA than in HS (p= 0.0019), whereasKIR2DL2andKIR2DS2were higher in RA than HS (p= 0.0004 andp= 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p= 0.0001,p= 0.0208 andp= 0.0300, respectively).Conclusions: The presence ofKIR2DL2,KIR2DS2and absence ofKIR2DL3are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest thatKIRscan be involved in RA susceptibility.

Association between KIR gene polymorphisms and rheumatoid arthritis susceptibility: A meta-analysis

“…Since then, eight case-control studies have been undertaken to identify the association between KIR polymorphisms and RA [14,20,21,[31][32][33][34][35], but the results were controversial. Based on cumulated evidence, we performed a meta-analysis with data from nine studies with a total of 1428 RA cases and 2115 healthy controls to reassess the associations.…”

“…1. Among the nine articles, four [20,22,32,33] were Caucasians, three [21,31,35] were from East Asian countries, one [34] was from India and one [14] was from Latin America. Because of the inadequate sample populations available for the Indian and Latin American group, we performed ethnicity-specific meta-analysis for Caucasian and East Asian populations.…”

“…HWE test was performed on genotype distribution of the control groups, only one [34] of them showed p > 0.05 in HWE, other articles could not be tested because of the lack of raw data. Six [14,20,31,32,34,35] of the nine studies were of high quality (NOS score P 7) and the other three scored six and are shown in Table 1.…”

“…Moreover, the onset of RA is likely to involve multiple genes, such as HLA-DRB1, KIRs, TRAF1/C5, STAT4, PTPN22 and CTLA4, etc. [12][13][14][15].…”

“…The associations between KIR genes and autoimmune diseases have been widely reported, such as rheumatoid arthritis (RA) [20][21][22], ankylosing spondylitis (AS) [23,24], systemic lupus erythematosus (SLE) [25], psoriasis [26,27], pemphigus foliaceus [28], scleroderma [25], multiple sclerosis [29], diabetes [30], etc. Plentiful case-control studies have investigated the association between these KIR gene polymorphisms and RA risk, but findings are not always consistent [14,[20][21][22][31][32][33][34][35]. In addition, until now, nobody performed a meta-analysis to estimate the association of KIR polymorphisms with RA risk.…”