Han Tae-Un, Lee Hye-Soon, Kang Changwon, Bae Sang-Cheol
Department of Biological Sciences, Korea Advanced Institute of Science and Technology , Daejeon , Korea and.
Autoimmunity. 2015;48(5):313-7. doi: 10.3109/08916934.2015.1016219. Epub 2015 Feb 24.
Two single-nucleotide polymorphisms (SNPs) in SLC22A4 encoding an organic cation/zwitterion transporter protein, rs2073838 (commonly called slc2F1) and rs3792876 (slc2F2), had been associated with susceptibility to rheumatoid arthritis (RA) in two Japanese and one recent Chinese studies but not in other two Japanese and six Caucasian studies. In this study, the two SNPs were genotyped for 2313 Korean participants and their associations with RA susceptibility and severity were examined. SNP association with RA susceptibility was tested among 1304 RA patients and 1009 healthy controls, and association with joint erosion among 1063 erosive and 241 non-erosive RA patients. Meta-analysis for RA susceptibility association was additionally performed using 10 previous studies and the current one. The two SNPs were almost perfectly correlated with each other (r(2 )= 0.98), and therefore only slc2F1 was tested for association. RA susceptibility association was not found in Koreans (p = 0.93), but still significant in meta-analysis of six Asian studies including this Korean study (p = 0.00036, odds ratio = 1.1) or all 11 studies additionally including five Caucasian studies (p = 0.00021, odds ratio = 1.1). In contrast, an association was found for RA severity in Koreans. The minor allele A was marginally associated with 1.5-fold increased risk of joint erosion among RA patients afflicted for ≤11 years (p = 0.025) or ≤7 years (p = 0.029), though not among patients with longer-standing RA. Accordingly, SLC22A4 was associated with joint erosion in not-very-longstanding RA, although RA susceptibility association was weak and its clinical significance was uncertain.
编码有机阳离子/两性离子转运蛋白的SLC22A4基因中的两个单核苷酸多态性（SNP），即rs2073838（通常称为slc2F1）和rs3792876（slc2F2），在两项日本研究和一项近期的中国研究中与类风湿性关节炎（RA）易感性相关，但在另外两项日本研究和六项高加索研究中未发现此关联。在本研究中，对2313名韩国参与者进行了这两个SNP的基因分型，并检测了它们与RA易感性和严重程度的关联。在1304名RA患者和1009名健康对照中测试了SNP与RA易感性的关联，在1063名侵蚀性RA患者和241名非侵蚀性RA患者中测试了与关节侵蚀的关联。另外使用之前的10项研究和本研究进行了RA易感性关联的荟萃分析。这两个SNP几乎完全相互关联（r(2 )= 0.98），因此仅测试了slc2F1的关联性。在韩国人中未发现RA易感性关联（p = 0.93），但在包括本韩国研究在内的六项亚洲研究的荟萃分析中仍具有显著性（p = 0.00036，优势比 = 1.1），或者在另外包括五项高加索研究的所有11项研究中也具有显著性（p = 0.00021，优势比 = 1.1）。相比之下，在韩国人中发现了与RA严重程度的关联。尽管在病程较长的RA患者中未发现，但对于病程≤11年（p = 0.025）或≤7年（p = 0.029）的RA患者，次要等位基因A与关节侵蚀风险增加1.5倍有微弱关联。因此，SLC22A4与病程不是很长的RA中的关节侵蚀相关，尽管RA易感性关联较弱且其临床意义尚不确定。
