Association of TIM-3 rs1036199 polymorphisms with the onset risk of rheumatoid arthritis：a Meta analysis

doi:10.3969/j.issn.1673-8640.2019.12.009

Abstract

Abstract:

Objective To evaluate the association of TIM-3 rs1036199 polymorphisms with the susceptibility of rheumatoid arthritis（RA）. Methods A systematic search of published studies related to the association of TIM-3 rs1036199 polymorphisms with RA was conducted in PubMed,Embase,Web of Science,CNKI,Wanfang and VIP databases（last updated on August 28,2018）. A Meta analysis was performed using STATA software. A total of 7 studies including 1 267 RA cases and 1 360 healthy subjects were enrolled. Results TIM-3 rs1036199 polymorphism was not associated with RA in allele comparison [G to T：odds ratio（OR）=1.44,95% confidence interval（CI） 0.73-2.82] and heterozygous comparison（GT to TT：OR=1.46,95%CI 0.70-3.06）. Subgroup analysis based on ethnicity demonstrated that TIM-3 rs1036199 polymorphism was associated with RA in Korean（G to T：OR=1.61,95%CI 1.20-2.14;GT to TT：OR=1.71,95%CI 1.26-2.32）. Subgroup analysis based on the source of control showed that TIM-3 rs1036199 polymorphism contributed to RA susceptibility in population based on case-control studies（G to T：OR=3.66,95%CI 1.90-7.04;GT to TT：OR=3.85,95%CI 1.98-7.48）. Conclusions The present studies reveal that TIM-3 rs1036199 polymorphism is associated with RA in Korean,while the association of TIM-3 rs1036199 with RA in Chinese remains uncertain.

Key words: Rheumatoid arthritis, TIM-3, Polymorphism, rs1036199

CLC Number:

R593.22

WANG Xing, MA Yan, WANG Shengnan, ZHANG Heqian, LIU Rongzeng. Association of TIM-3 rs1036199 polymorphisms with the onset risk of rheumatoid arthritis：a Meta analysis[J]. Laboratory Medicine, 2019, 34(12): 1101-1106.

Figures/Tables 5

References 23

[1]	CALABRESI E,PETRELLI F,BONIFACIO A F,et al.One year in review 2018:pathogenesis of rheumatoid arthritis[J]. Clin Exp Rheumatol,2018,36(2):175-184.
[2]	李云春,钟利,王悦,等. 类风湿性关节炎患者红细胞体积分布宽度及相关炎性因子与病情活动度的相关性[J]. 检验医学,2017,32(4):304-307.
[3]	曾惠琼,扶忠超,黄新民,等. D-二聚体、纤维蛋白原、转铁蛋白水平对类风湿关节炎的临床意义[J]. 检验医学,2017,32(10):883-885.
[4]	SMOLEN J S,ALETAHA D,BARTON A,et al.Rheumatoid arthritis[J]. Nat Rev Dis Primers,2018,4:18001.
[5]	YOO Y J,GAO G,ZHANG K.Case-control association analysis of rheumatoid arthritis with candidate genes using related cases[J]. BMC Proc,2007,1(Suppl 1):S33.
[6]	XU J,YANG Y,LIU X,et al.Genetic variation and significant association of polymorphism rs7700944 G>A of TIM-4 gene with rheumatoid arthritis susceptibility in Chinese Han and Hui populations[J]. Int J Immunogenet,2012,39(5):409-413.
[7]	XU J R,YANG Y,LIU X M,et al.Polymorphisms of the TIM-1 gene are associated with rheumatoid arthritis in the Chinese Hui minority ethnic population[J]. Genet Mol Res,2012,11(1):61-69.
[8]	MOSAAD Y M,EL-BASSIONY S R,EL-GHAWEET A E,et al. TIM-1 rs41297579 G>A(-1454) and TIM-4 rs7700944 gene polymorphisms as possible risk factor for rheumatoid arthritis:relation to activity and severity[J]. Int J Immunogenet,2015,42(4):254-264.
[9]	CHAE S C,SONG J H,SHIM S C,et al.The exon 4 variations of Tim-1 gene are associated with rheumatoid arthritis in a Korean population[J]. Biochem Biophys Res Commun,2004,315(4):971-975.
[10]	CHAE S C,PARK Y R,SONG J H,et al.The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population[J]. Immunogenetics,2005,56(10):696-701.
[11]	GORMAN J V,COLGAN J D.Regulation of T cell responses by the receptor molecule Tim-3[J]. Immunol Res,2014,59(1-3):56-65.
[12]	GORMAN J V,STARBECK-MILLER G,PHAM N L L,et al. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection[J]. J Immunol,2014,192(7):3133-3142.
[13]	FOURCADE J,SUN Z,PAGLIANO O,et al.PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8+ T cells induced by melanoma vaccines[J]. Cancer Res,2014,74(4):1045-1055.
[14]	WANG F,HOU H,XU L,et al.Tim-3 signaling pathway as a novel negative mediator in lipopolysaccharide-induced endotoxic shock[J]. Hum Immunol,2014,75(5):470-478.
[15]	CHAE S C,PARK Y R,SHIM S C,et al.The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis[J]. Immunol Lett,2004,95(1):91-95.
[16]	XU J,YANG Y,LIU X,et al.The -1541 C>T and +4259 G>T of TIM-3 polymorphisms are associated with rheumatoid arthritis susceptibility in a Chinese Hui population[J]. Int J Immunogenet,2011,38(6):513-518.
[17]	SONG Y W,IM C H,PARK J H,et al.T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status[J]. Hum Immunol,2011,72(8):652-655.
[18]	张才成,吴健民,崔天盆,等. Tim-3启动子区基因多态性与类风湿关节炎之间关系的研究[J]. 中华风湿病学杂志,2005,9(9):526-529.
[19]	李晓凤. 青海地区汉、藏族人群类风湿关节炎的Tim-3基因多态性研究[D]. 西宁:青海大学,2014.
[20]	李琳芸,彭长华,梅冰,等. 中国人群强直性脊柱炎与ERAP-1基因多态性的相关性Meta分析[J]. 检验医学,2018,33(6):481-485.
[21]	MEYERS J H,SABATOS C A,CHAKRAVARTI S,et al.The TIM gene family regulates autoimmune and allergic diseases[J]. Trends Mol Med,2005,11(8):362-369.
[22]	ANDERSON A C,ANDERSON D E.TIM-3 in autoimmunity[J]. Curr Opin Immunol,2006,18(6):665-669.
[23]	CHAE S C,SONG J H,POUNSAMBATH P,et al.Molecular variations in Th1-specific cell surface gene Tim-3[J]. Exp Mol Med,2004,36(3):274-278.

文献	年份（年）	人群	基因分型方法	对照来源	病例组			对照组			Hardy-Weinberg 平衡
文献	年份（年）	人群	基因分型方法	对照来源	TT	TG	GG	TT	TG	GG	Hardy-Weinberg 平衡
CHAE等^[15]	2004	韩国人	SBE	PB	203	93	0	256	63	0	0.050 0
XU等^[16]	2011	中国回族	PCR-SSP	PB	198	28	0	224	7	0	0.815 0
XU等^[16]	2011	中国汉族	PCR-SSP	PB	90	13	0	103	5	0	0.806 0
SONG等^[17]	2011	韩国人	TaqMan	HB	335	31	0	365	24	0	0.530 0
张方成等^[18]	2006	中国汉族	ASPCR	HB	100	15	0	96	4	0	0.838 3
李晓凤^[19]	2014	中国汉族	PCR-RFLP	HB	96	4	1	77	34	0	0.056 7
李晓凤^[19]	2014	中国藏族	PCR-RFLP	HB	56	4	0	94	7	1	0.059 9

文献	年份（年）	人群	基因分型方法	对照来源	病例组			对照组			Hardy-Weinberg 平衡
文献	年份（年）	人群	基因分型方法	对照来源	TT	TG	GG	TT	TG	GG	Hardy-Weinberg 平衡
CHAE等^[15]	2004	韩国人	SBE	PB	203	93	0	256	63	0	0.050 0
XU等^[16]	2011	中国回族	PCR-SSP	PB	198	28	0	224	7	0	0.815 0
XU等^[16]	2011	中国汉族	PCR-SSP	PB	90	13	0	103	5	0	0.806 0
SONG等^[17]	2011	韩国人	TaqMan	HB	335	31	0	365	24	0	0.530 0
张方成等^[18]	2006	中国汉族	ASPCR	HB	100	15	0	96	4	0	0.838 3
李晓凤^[19]	2014	中国汉族	PCR-RFLP	HB	96	4	1	77	34	0	0.056 7
李晓凤^[19]	2014	中国藏族	PCR-RFLP	HB	56	4	0	94	7	1	0.059 9

变量	例数	GT相对于TT			G相对于T
变量	例数	OR（95%CI）	P值	I²（%）	OR（95%CI）	P值	I²（%）
人群
中国人	5	1.39（0.38~5.14）	0.000	88.0	1.36（0.32~5.80）	0.000	89.2
韩国人	2	1.61（1.20~2.14）^*	0.536	0.0	1.71（1.26~2.32）^*	0.410	0.0
对照来源
HB	5	1.02（0.45~2.30）	0.000	84.9	1.01（0.40~2.54）	0.000	86.7
PB	2	3.66（1.90~7.04）^*	0.547	0.0	3.85（1.98~7.48）^*	0.547	0.0
基因分型方法
PCR-RFLP	2	0.34（0.08~1.44）	0.050	73.9	0.29（0.03~2.91）	0.006	86.8
PCR-SSP	2	3.66（1.90~7.04）^*	0.547	0.0	3.85（1.98~7.48）^*	0.547	0.0
其他分型方法	3	1.68（1.27~2.24）^*	0.363	1.3	1.80（1.30~2.50）^*	0.329	1.0
合计	7	1.44（0.73~2.82）	0.000	82.7	1.46（0.70~3.06）	0.000	84.0

变量	例数	GT相对于TT			G相对于T
变量	例数	OR（95%CI）	P值	I²（%）	OR（95%CI）	P值	I²（%）
人群
中国人	5	1.39（0.38~5.14）	0.000	88.0	1.36（0.32~5.80）	0.000	89.2
韩国人	2	1.61（1.20~2.14）^*	0.536	0.0	1.71（1.26~2.32）^*	0.410	0.0
对照来源
HB	5	1.02（0.45~2.30）	0.000	84.9	1.01（0.40~2.54）	0.000	86.7
PB	2	3.66（1.90~7.04）^*	0.547	0.0	3.85（1.98~7.48）^*	0.547	0.0
基因分型方法
PCR-RFLP	2	0.34（0.08~1.44）	0.050	73.9	0.29（0.03~2.91）	0.006	86.8
PCR-SSP	2	3.66（1.90~7.04）^*	0.547	0.0	3.85（1.98~7.48）^*	0.547	0.0
其他分型方法	3	1.68（1.27~2.24）^*	0.363	1.3	1.80（1.30~2.50）^*	0.329	1.0
合计	7	1.44（0.73~2.82）	0.000	82.7	1.46（0.70~3.06）	0.000	84.0