Abstract
BackgroundRheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. The goal of our meta-analysis was to summarize the contribution of TAP2 polymorphisms to the risk of RA.MethodsMeta-analyses were performed between RA and 3 TAP2 coding polymorphisms that comprised TAP2-379Ile > Val (rs1800454), TAP2-565Ala > Thr (rs2228396) and TAP2-665Thr > Ala (rs241447). The meta-analyses were involved with 9 studies (24 individual studies) among 973 cases and 965 controls.ResultsMeta-analyses showed that TAP2-379Ile allele was significantly associated with an increased risk of RA (p = 0.0002, odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.18-1.74). This association was further shown only in the dominant model (p = 0.006, OR = 1.59, 95% CI = 1.14-2.22). Subgroup analyses by ethnicity revealed that the association of TAP2-379Ile was significant in Asians (p = 0.03, OR = 1.38, 95% CI = 1.04-1.83). In addition, another significant association of TAP2-565Thr allele with RA was observed in Europeans (p = 0.002, OR = 1.62, 95% CI = 1.20-2.20).ConclusionsOur meta-analyses suggested that TAP2-379Ile allele was significantly associated with a 59% increased risk in the dominant effect model. Subgroup analyses by ethnicity showed that TAP2-379-Ile increased the risk of RA by 38% in Asians and TAP2-565Thr increased the risk of RA by 38% in Europeans.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2097080313124700
Highlights
Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci
We tested the associations between 3 transporter associated with antigen processing 2 (TAP2) polymorphisms and RA disease
Subgroup analysis by ethnicity showed that this significant association was only found in Asians (p = 0.03, odds ratios (ORs) = 1.38, 95% 95% confidence intervals (CIs) = 1.04-1.83, Table 3 and Figure 2) but not in Europeans (p = 0.16, Table 3)
Summary
Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. Family-based studies demonstrated that genetic factors played a more important role in the development of RA than environmental factors [5,6]. Consistent association was found between human leukocyte antigen (HLA) loci and RA [7]. The transporter associated with antigen processing 2 (TAP2) gene encodes transporter 2, ATP-binding cassette, sub-family B (MDR/ TAP) that is a major histocompatibility complex (MHC) gene located between HLA-DP and HLA-DQ [8]. TAP2 has been shown to play an important role in the HLA-associated diseases and immune response [11]
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