CD40基因多态性及血清水平与系统性红斑狼疮发病机制的相关研究

中华皮肤科杂志 ›› 2016, Vol. 49 ›› Issue (1): 12-16.

CD40基因多态性及血清水平与系统性红斑狼疮发病机制的相关研究

吴成将¹,袁秋然¹,莫益姣¹,梁丽群¹,王春芳¹,蒋远文¹,蓝艳²

1. 右江民族医学院附属医院检验科
2. 右江民族医学院附属医院皮肤科

收稿日期:2015-06-04 修回日期:2015-07-29 出版日期:2016-01-15 发布日期:2015-12-31
通讯作者: 蓝艳 E-mail:2543430342@qq.com
基金资助:
国家自然科学基金资助项目;广西卫生厅重点课题

Association of CD40 gene polymorphisms and serum CD40 levels with the pathogenesis of systemic lupus erythematosus

Received:2015-06-04 Revised:2015-07-29 Online:2016-01-15 Published:2015-12-31

摘要/Abstract

摘要：

目的探讨CD40基因单核苷酸多态性（SNP）及其单倍型与SLE易感性的相关性，分析CD40基因型及血清水平与系统性红斑狼疮（SLE）的相关性。方法单碱基延伸的PCR技术（PCR-SBE）和DNA测序法分析205例SLE患者和220例健康对照CD40基因rs1883832 C/T、 rs13040307 C/T、rs752118 C/T 和rs3765459 G/A的多态性，同时用ELISA检测血清CD40水平。结果与健康对照组相比，SLE组血清CD40水平显著增高（P < 0.05）。SLE组与健康对照组CD40基因rs1883832 C/T位点基因型和等位基因频率比较，差异有统计学意义（P < 0.01）。等位基因频率的相对风险分析后发现，携带有rs1883832 T等位基因的受试者患有SLE的风险是rs1883832 C等位基因的1.517倍（OR = 1.517，95% CI 1.157 ~ 1.990，P = 0.003）；携带rs1883832 T等位基因的SLE患者血清CD40水平与不携带者相比，结果显著增高（P < 0.01）。通过联合基因型分析发现，SLE组中携带单倍型TCCA的患者较健康对照组显著增加了发病的风险（OR = 2.322，95% CI 1.181 ~ 4.564，P = 0.012）。结论 CD40基因rs1883832 C/T多态性和TCCA单倍型与SLE的发病有相关性，其中rs1883832 T等位基因可能是SLE的遗传易感基因。

Abstract:

Wu Chengjiang, Yuan Qiuran, Mo Yijiao, Liang Liqun, Wang Chunfang, Jiang Yuanwen, Lan Yan Department of Clinical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China （Wu CJ, Yuan QR, Mo YJ, Liang LQ, Wang CF）; Department of Dermatology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China （Jiang YW, Lan Y） Corresponding author: Lan Yan, Email: yylanyan@163.com 【Abstract】 Objective To explore the association of CD40 gene single nucleotide polymorphisms （SNPs） and haplotypes with the susceptibility to systemic lupus erythematosus （SLE）, as well as the association of serum levels and genotypes of CD40 with the occurrence of SLE. Methods A multiplex PCR single-base extension assay （PCR-SBE） and DNA sequencing were performed to analyze 4 SNPs of the CD40 gene, including rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A, in 205 patients with SLE （SLE group） and 220 healthy human controls （control group）. Enzyme-linked immunosorbent assay （ELISA） was conducted to measure serum levels of CD40 in these subjects. Results Compared with the control group, the SLE group showed significantly increased serum levels of CD40 （P < 0.05）. There were significant differences in genotype and allele frequencies of the SNP rs1883832 C/T in the CD40 gene between the SLE group and control group （all P < 0.01）. Relative risk analysis showed that the risk of developing SLE in rs1883832 T allele carriers was 1.517 times that in rs1883832 C allele carriers （OR = 1.517, 95% CI: 1.157 - 1.990, P = 0.003）. Moreover, serum levels of CD40 were significantly higher in rs1883832 T allele carriers than in rs1883832 C allele carriers （P < 0.01）. The risk of developing SLE was significantly increased in TCCA haplotype carriers compared with the healthy controls （OR = 2.322, 95% CI: 1.181 - 4.564, P = 0.012）. Conclusion The CD40 gene rs1883832 C/T polymorphism and its TCCA haplotype were both associated with the occurrence of SLE, and the rs1883832 T allele may be a gene predisposing to SLE.

吴成将袁秋然莫益姣梁丽群王春芳蒋远文蓝艳. CD40基因多态性及血清水平与系统性红斑狼疮发病机制的相关研究[J]. 中华皮肤科杂志, 2016, 49(1): 12-16.doi:

参考文献 14

［1］	Asano NM, Angelo HD, da Silva HA, et al. Interleukin⁃6 promoter polymorphisms ⁃174 G/C in Brazilian patients with systemic lupus erythematosus［J］. Hum Immunol, 2013, 74（9）: 1153⁃1156. DOI: 10.1016/j.humimm.2013.05.015.
［2］	Liu J, Liu J, Ni J, et al. Association of UBASH3A gene polymor⁃phisms and systemic lupus erythematosus in a Chinese population［J］. Gene, 2015, 565（1）: 116⁃121. DOI: 10.1016/j.gene.2015.04.005.
［3］	温斯健, 吴飞云, 林有坤, 等. 广西壮族、汉族SLE与Toll样受体9基因多态性研究［J］. 中华皮肤科杂志, 2014, 47（6）: 404⁃408. DOI: 10.3760/cma.j.issn.0412⁃4030.2014.06.008.
	Wen SJ, Wu FY, Lin YK, et al. Associations between Toll⁃like receptor 9 gene polymorphisms and systemic lupus erythematosus in Guangxi Zhuang and Han populations［J］. Chin J Dermatol, 2014, 47（6）: 404⁃408. DOI: 10.3760/cma.j.issn.0412⁃4030.2014. 06.008.
［4］	Raychaudhuri S, Remmers EF, Lee AT, et al. Common variants at CD40 and other loci confer risk of rheumatoid arthritis［J］. Nat Genet, 2008, 40（10）: 1216⁃1223. DOI: 10.1038/ng.233.
［5］	Li M, Sun H, Liu S, et al. CD40 C/T⁃1 polymorphism plays different roles in Graves′ disease and Hashimoto′s thyroiditis: a meta⁃analysis［J］. Endocr J, 2012, 59（12）: 1041⁃1050.
［6］	蓝艳, 韦叶生, 杜诗库. E选择素基因多态性与广西壮族系统性红斑狼疮的相关性研究［J］. 中华皮肤科杂志, 2005, 38（1）: 11⁃13. DOI: 10.3760/j.issn:0412⁃4030.2005.01.005.
	Lan Y, Wei YS, Du SK. Association of the E⁃selectin polymorphism with systemic lupus erythematosus in the Ethnic Zhuang population from Guangxi Province［J］. Chin J Dermatol, 2005, 38 （1）: 11⁃13. DOI: 10.3760/j.issn:0412⁃4030.2005.01.005.
［7］	蓝艳, 蒋远文, 唐秀生, 等. 白细胞介素27基因多态性与广西壮族系统性红斑狼疮的相关性研究［J］. 中华皮肤科杂志, 2011, 44（8）: 578⁃580. DOI: 10.3760/cma.j.issn.0412⁃4030.2011.08.016.
	Lan Y, Jiang YW, Tang XS, et al. Association of interleukin⁃27 gene polymorphisms with genetic susceptibility to systematic lupus erythematosus in Guangxi Zhuang population［J］. Chin J Dermatol, 2011, 44（8）: 578⁃580. DOI: 10.3760/cma.j.issn.0412⁃4030.2011. 08.016.
［8］	Duffau P, Seneschal J, Nicco C, et al. Platelet CD154 potentiates interferon⁃alpha secretion by plasmacytoid dendritic cells in systemic lupus erythematosus［J］. Sci Transl Med, 2010, 2（47）:47ra63. DOI: 10.1126/scitranslmed.3001001.
［9］	Koshy M, Berger D, Crow MK. Increased of CD40 ligand on systemic lupus erythematosus lymphocytes［J］. J Clin Invest, 1996, 98（3）: 826⁃837. DOI: 10.1172/JCI118855.
［10］	Boumpas DT, Furie R, Manzi S, et al. A short course of BG9588（anti⁃CD40 ligand antibody） improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis［J］. Arthritis Rheum, 2003, 48（3）: 719⁃727.
［11］	Vazgiourakis VM, Zervou MI, Choulaki C, et al. A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 : implications for the pathogenesis［J］. Ann Rheum Dis, 2011, 70（12）: 2184⁃2190. DOI: 10.1136/ard.2010.146530.
［12］	Piotrowski P, Lianeri M, Wudarski M, et al. Single nucleotide polymorphism of CD40 region and the risk of systemic lupus erythematosus［J］. Lupus, 2013, 22（3）: 233⁃237. DOI: 10.1177/0961203312470184.
［13］	Lee YH, Bae SC, Choi SJ, et al. Associations between the functional CD40 rs4810485 G/T polymorphism and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta⁃analysis［J］. Lupus, 2015, 24（11）: 1177⁃1183. DOI: 10.1177/0961203315583543.
［14］	Joo YB, Park BL, Shin HD, et al. Association of genetic polymor⁃phisms in CD40 with susceptibility to SLE in the Korean population［J］. Rheumatology （Oxford）, 2013, 52（4）: 623⁃630. DOI: 10.1093/rheumatology/kes339.