SLE患者血清中Tim-3表达及其启动子区-1516G/T位点基因多态性分析
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摘要
目的了解系统性红斑狼疮(systemiclupuserythematosus,SLE)患者血清中T细胞免疫球蛋白粘蛋白分子-3(T cell immunoglobulin domain and mucin domain protein-3,Tim-3)水平表达情况,并探索其启动子区-1516G/T位点基因单核苷酸多态性(singlenucleotidepolymorphisms,SNPs)与深圳地区SLE患者之间的遗传易感性。方法收集2015年3月～2018年11月来深圳市福田区风湿病专科医院就诊并确诊为SLE患者105例为研究组,并选择同期来医院体检的健康人群120名为对照组,分别采用酶联免疫吸附法(ELISA)检测Tim-3含量,同时采用聚合酶链反应(PCR-RFLP)技术对Tim-3启动子区-1516G/T位点基因SNPs多态性进行分析。结果 SLE组患者血清中Tim-3水平为29.61±8.34pg/mL,明显高于对照组健康人群的13.97±4.28pg/mL,差异有统计学意义(t=3.0251,P<0.05);SLE组患者Tim-3启动子区-1516G/TTT基因型和T等位基因检出率分别为18.10%和33.33%,明显高于对照组的5.83%和20.00%,差异有统计学意义(χ~2=3.0241～4.7265,P<0.05);TT基因型SLE患者血清中Tim-3浓度为38.02±11.63pg/mL,明显高于GT基因型的31.24±9.06pg/mL和GG基因型的27.50±7.32pg/mL,差异有统计学意义(t=2.1954～2.8162,P<0.05)。结论 Tim-3水平在SLE患者血清中呈高度表达,尤其TT基因型SLE患者增加更为明显,且Tim-3启动子区1516G/T位点基因多态性变异与深圳地区SLE遗传易感性有关,其中TT基因型和T等位基因可能是本地区SLE患者发病的易感基因之一。
Objective:To understand the expression level of T cell immunoglobulin domain and mucin domain protein-3 in serum of patients with systemic lupus erythematosus,and explore the genetic susceptibility of single nucleotide polymorphisms in promoter region-1516 G/T locus to SLE patients in shenzhen. Methods:Collected in March 2015 to November 2018 to shenzhen futian district rheumatism specialist hospital and diagnosed with SLE patients 105 cases for the study group,and select the same period to hospital medical healthy people 120 called the control group,respectively,using the method of enzymelinked immunosorbent(ELISA)to detect the contents of Tim-3,at the same time using polymerase chain reaction(PCR-RFLP)technique to Tim-3 promoter region-1516-G/T SNPs loci gene polymorphisms were analyzed. Results:The serum level of tim-3 in SLE group was 29.61±8.34 pg/mL,significantly higher than 13.97±4.28 pg/mL in healthy control group,and the difference was statistically significant(t=3.0251,P<0.05). The detection rates of tim-3 promoter region-1516 G/T TT genotype and T allele in SLE group were 18.10% and 33.33%,respectively,significantly higher than 5.83% and 20.00% in control group,respectively,and the differences were statistically significant(χ~2=3.0241～4.7265,P<0.05). The serum concentration of tim-3 in TT genotype SLE patients was 38.02±11.63 pg/mL,significantly higher than 31.24±9.06 pg/mL of GT genotype and27.50 + 7.32 pg/mL of GG genotype,The difference was statistically significant(t=2.1954～2.8162,P<0.05). Conclusion:Tim-3 level is highly expressed in the serum of SLE patients,especially the increase of TT genotype SLE patients is more obvious,and the polymorphism variation at 1516 G/T site of tim-3 promoter region is related to the genetic susceptibility of SLE in shenzhen region,among which TT genotype and T allele may be one of the susceptibility genes of SLE patients in this region.
Objective:To understand the expression level of T cell immunoglobulin domain and mucin domain protein-3 in serum of patients with systemic lupus erythematosus,and explore the genetic susceptibility of single nucleotide polymorphisms in promoter region-1516 G/T locus to SLE patients in shenzhen. Methods:Collected in March 2015 to November 2018 to shenzhen futian district rheumatism specialist hospital and diagnosed with SLE patients 105 cases for the study group,and select the same period to hospital medical healthy people 120 called the control group,respectively,using the method of enzymelinked immunosorbent(ELISA)to detect the contents of Tim-3,at the same time using polymerase chain reaction(PCR-RFLP)technique to Tim-3 promoter region-1516-G/T SNPs loci gene polymorphisms were analyzed. Results:The serum level of tim-3 in SLE group was 29.61±8.34 pg/mL,significantly higher than 13.97±4.28 pg/mL in healthy control group,and the difference was statistically significant(t=3.0251,P<0.05). The detection rates of tim-3 promoter region-1516 G/T TT genotype and T allele in SLE group were 18.10% and 33.33%,respectively,significantly higher than 5.83% and 20.00% in control group,respectively,and the differences were statistically significant(χ~2=3.0241～4.7265,P<0.05). The serum concentration of tim-3 in TT genotype SLE patients was 38.02±11.63 pg/mL,significantly higher than 31.24±9.06 pg/mL of GT genotype and27.50 + 7.32 pg/mL of GG genotype,The difference was statistically significant(t=2.1954～2.8162,P<0.05). Conclusion:Tim-3 level is highly expressed in the serum of SLE patients,especially the increase of TT genotype SLE patients is more obvious,and the polymorphism variation at 1516 G/T site of tim-3 promoter region is related to the genetic susceptibility of SLE in shenzhen region,among which TT genotype and T allele may be one of the susceptibility genes of SLE patients in this region.
引文
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[8]秦岭,邱志锋,谢静,等.系统性红斑狼疮合并机会性感染的疾病普及其外周血淋巴细胞亚群特点分析[J].中华内科杂志,2018,57(1):32-36.
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[10]JIAO Q,QIAN Q,ZHAO Z,et al.Expression of human T cell immunoglobulin domain and mucin-3(TIM-3)and TIM-3ligands in peripheral blood from patients with systemic lupus erythematosus[J].Arch Dermatol Res,2016,308(8):553.
[11]金来润,袁慧.Tim-3在系统性红斑狼疮中的研究进展[J].湖北科技学院学报(医学版),2017,31(5):451-455.
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[15]喻少波,范小杰,周子朋,等.SLE患者外周血单个核细胞miR-21,miR-155表达变化及其机制[J].山东医药,2018,58(20):58-60.
[16]熊勤.Tim-1蛋白在SLE患者血清中的表达及其基因多态性分析[J].数理医药学杂志,2016,29(1):6-8.
[17]陈婉婷,彭传梅,高辉.Tim基因家族与系统性红斑狼疮关系的研究进展[J].国际检验医学杂志,2015,36(11):1599-1601.
[18]高永利,叶明,高乐,等.CD40基因-1C/T位点基因多态性与系统性红斑狼疮发病、临床特征及SLEDAI指数的关系[J].临床和实验医学杂志,2017,16(23):2332-2335.
[19]高辉,彭传梅,付晓野,等.云南汉族人群Tim-3启动子区-1516G>T位点多态性与系统性红斑狼疮关联性研究[J].检验医学与临床,2015,12(8):1034-1036.
[20]LI W X,CHENG M,YUAN H,et al.Polymorphisms of the TIM-1and TIM-3 genes are not associated with sysemic lupus erythematosus in a Chinese population[J].Mutagenesis,2011,26(4):507.
[21]李敏,李雪锋,郭毅飞,等.白细胞介素-17、单核细胞趋化蛋白-1与系统性红斑狼疮患者亚临床动脉粥样硬化的关系[J].国际检验医学杂志,2018,39(16):1963-1967,1971.
[2]Cai X,Li X,Lin X,et al.Expression of regulatory B cells in peripheral blood of patients with systemic lupus erythematosus[J].Zhonghua Yi Xue Za Zhi,2015,95(17):1310-1313.
[3]陈向华,王建吉,耿学丽,等.Tim-1蛋白表达及其基因多态性与系统性红斑狼疮患者营养功能的相关性[J].中国医科大学学报,2017,46(7):623-627.
[4]曾转萍,廖日房,庾永基,等.广州市系统性红斑狼疮患者发生感染的影响因素研究[J].中华疾病控制杂志,2015,19(2):158-161.
[5]鄢海波,赵令,马宁,等.汉族人系统性红斑狼疮和狼疮肾炎与IL-22受体基因多态性的关系[J].中国现代医学杂志,2017,27(9):44-48.
[6]张昀,刘淑芬,曾学军.中国汉族人群FcγRIII A F158V基因多态性与系统性红斑狼疮及狼疮肾炎相关[J].基础医学与临床,2017,37(5):709-713.
[7]谷园园,邹延峰,徐建华,等.中国人群中Hsp90AB1基因多态性和SLE发病的关联研究[J].安徽医科大学学报,2016,51(8):1151-1155.
[8]秦岭,邱志锋,谢静,等.系统性红斑狼疮合并机会性感染的疾病普及其外周血淋巴细胞亚群特点分析[J].中华内科杂志,2018,57(1):32-36.
[9]董玉梅.系统性红斑狼疮的诊断标准及治疗研究进展[J].临床医药文献杂志,2017,4(44):8711-8712.
[10]JIAO Q,QIAN Q,ZHAO Z,et al.Expression of human T cell immunoglobulin domain and mucin-3(TIM-3)and TIM-3ligands in peripheral blood from patients with systemic lupus erythematosus[J].Arch Dermatol Res,2016,308(8):553.
[11]金来润,袁慧.Tim-3在系统性红斑狼疮中的研究进展[J].湖北科技学院学报(医学版),2017,31(5):451-455.
[12]GUO L,YANG X,XIA Q,et al.Expression of human T ell immunoglobulin domain and mucin-3(TIM-3)on kidney tissue from systemic lupus erythematosus(SLE)patients[J].Clin Exp Med,2014,14(4):383.
[13]ZHENG H,GUO X,TIAN Q,et al.Distinct role of Tim-3 in systemic lupus erythematosus and clear cell renal cell carcinoma[J].Int J Clin Exp Med,2015,8(5):7029.
[14]SONG L J,WANG X,WANG X P,et al.Increased Tim-3expression on peripheral T lymphocyte subsets and association with higher disease activity in systemic lupus erythematosus[J].Diagn Pathol,2015,10:71.
[15]喻少波,范小杰,周子朋,等.SLE患者外周血单个核细胞miR-21,miR-155表达变化及其机制[J].山东医药,2018,58(20):58-60.
[16]熊勤.Tim-1蛋白在SLE患者血清中的表达及其基因多态性分析[J].数理医药学杂志,2016,29(1):6-8.
[17]陈婉婷,彭传梅,高辉.Tim基因家族与系统性红斑狼疮关系的研究进展[J].国际检验医学杂志,2015,36(11):1599-1601.
[18]高永利,叶明,高乐,等.CD40基因-1C/T位点基因多态性与系统性红斑狼疮发病、临床特征及SLEDAI指数的关系[J].临床和实验医学杂志,2017,16(23):2332-2335.
[19]高辉,彭传梅,付晓野,等.云南汉族人群Tim-3启动子区-1516G>T位点多态性与系统性红斑狼疮关联性研究[J].检验医学与临床,2015,12(8):1034-1036.
[20]LI W X,CHENG M,YUAN H,et al.Polymorphisms of the TIM-1and TIM-3 genes are not associated with sysemic lupus erythematosus in a Chinese population[J].Mutagenesis,2011,26(4):507.
[21]李敏,李雪锋,郭毅飞,等.白细胞介素-17、单核细胞趋化蛋白-1与系统性红斑狼疮患者亚临床动脉粥样硬化的关系[J].国际检验医学杂志,2018,39(16):1963-1967,1971.