广西壮族、汉族系统性红斑狼疮与Toll样受体9基因多态性研究

中华皮肤科杂志 ›› 2014, Vol. 47 ›› Issue (6): 404-408.

广西壮族、汉族系统性红斑狼疮与Toll样受体9基因多态性研究

温斯健¹,²,吴飞云¹,林有坤¹,方玲³

1. 广西医科大学第一附属医院皮肤性病科
2. 广西医科大学第一附属医院皮肤性病科（现在本所读研）
3. 广西医科大学细胞生物学与遗传学教研室

收稿日期:2013-08-26 修回日期:2013-12-05 发布日期:2014-06-01
通讯作者: 林有坤 E-mail:linyoukun7@yahoo.com.cn
基金资助:
广西自然科学基金

Associations between Toll-like receptor 9 gene polymorphisms and systemic lupus erythematosus in Guangxi Zhuang and Han populations

Received:2013-08-26 Revised:2013-12-05 Published:2014-06-01

摘要/Abstract

摘要： 目的探讨TLR9单核苷酸多态性与广西系统性红斑狼疮（SLE）患者发病的相关性，以及其在壮族、汉两个民族间的差异。方法聚合酶链反应-限制性酶切技术、聚合酶链反应-限制性片段长度多态性分析技术（PCR-RFLP）对97例广西SLE患者和202例广西健康对照者的TLR9基因多态性进行检测，分析其基因型和等位基因频率与SLE部分临床实验室指标的关联性，并比较两民族间的差异。结果 TLR9 rs352140CC、CT、TT基因型频率在汉族SLE组与汉族对照组中分别为42.9%、41.1%、16.1%和38.3%、55.8%、5.8%，差异有统计学意义（P < 0.05），其C、T等位基因频率差异无统计学意义（P > 0.05）。TLR9rs352140 C/T基因型频率和等位基因频率在壮族SLE组与壮族健康对照组间、壮族SLE组与汉族SLE组间差异无统计学意义（均P > 0.05）。TLR9 rs352140TT基因型频率在ds-DNA阳性组比阴性组高（P < 0.05），而T等位基因频率在两组间差异无统计学意义（P > 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在SLEDAI ≥ 9组比SLEDAI < 9组高，差异有统计学意义（均P < 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在ANA阳性组与阴性组间差异无统计学意义（均P > 0.05）。结论 TLR9 rs352140基因多态性可能与广西汉族人SLE的易感性有关， TLR9基因多态性与部分SLE指标可能具有相关性。

关键词: 红斑狼疮，系统性, Toll样受体9, 多态性，单核苷酸, 壮族, 汉族

Abstract: Wen Sijian*, Wu Feiyun, Lin Youkun, Fang Ling. *Department of Dermatology and Venereology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China Corresponding author: Lin Youkun, Email: linyoukun7@aliyun.com 【Abstract】 Objective To assess the association between Toll-like receptor 9 （TLR9） gene single nucleotide polymorphisms （SNPs） and systemic lupus erythematosus （SLE） development in Guangxi Zhuang and Han populations, as well as the difference in TLR9 SNPs between the two populations. Methods Totally, 41 SLE patients of Zhuang nationality and 56 of Han nationality, as well as 82 healthy checkup examinees of Zhuang nationality and 120 of Han nationality were enrolled in this study. Venous blood samples were obtained from all of these subjects and subjected to DNA extraction. The single nucleotide polymorphisms in TLR9 gene were detected by PCR-restriction fragment length polymorphism（PCR-RFLP） analysis followed by direct sequencing. Chi-square test and adjusted Chi-square test were conducted to assess the relationship between the genotype and allele frequencies of TLR9 SNPs and some clinical and laboratory parameters of patients with SLE, as well as the differences in genotype and allele frequencies of TLR9 SNPs between the two populations. Results The frequencies of CC, CT and TT genotypes of TLR9 SNP rs352140 were 42.9%, 41.1% and 16.1% respectively in the patients of Han nationality, compared to 38.3%, 55.8% and 5.8% in the healthy controls of Han nationality （all P < 0.05）, but no significant difference was observed in the frequency of C or T allele of the SNP rs352140 between the patients and controls of Han nationality （both P > 0.05）. There was no significant difference in the genotype or allele frequency of TLR9 SNP rs352140 between the patients and healthy controls of Zhuang nationality, or between the patients of Han nationality and Zhuang nationality （all P > 0.05）. The patients with anti-dsDNA antibodies showed a significantly higher frequency of TT genotype （P < 0.05）, but similar T allele frequency at TLR9 SNP rs352140 （P > 0.05） compared with those without. The frequencies of both TT genotype and T allele of TLR9 SNP rs352140 were significantly increased in the patients with a SLE disease activity index （SLEDAI） ≥ 9 compared with those with a SLEDAI < 9 （both P < 0.05）. There was no statistical difference in either the TT genotype or the T allele frequency at TLR9 SNP rs352140 between antinuclear antibody-positive and -negative patients with SLE（both P > 0.05）. Conclusions The TLR9 SNP rs352140 is correlated with several clinical and laboratory parameters of SLE, and might contribute to the susceptibility to SLE in Guangxi Han population.

Key words: Lupus erythematosus, systemic, Toll-like receptor 9, Polymorphism, single nucleotide, Zhuang nationality, Han nationality

温斯健吴飞云林有坤方玲. 广西壮族、汉族系统性红斑狼疮与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:

参考文献

[1]Rahman AH, Eisenberg RA.The role of toll like receptors in systemic lupus erythematosus[J].Springer Semin Immunopathol, 2006, 28(2):131-
[2]Goeken J A Layer TFleenor S et al.B-cell receptor for antigen modulates B-cell responses to complex TLR9 agonists and antagonists:implications for systemic lupus erythematosus.Lupus, 2010, 19:1290-1301
[3]Patole PS, Pawar RD, LechM, et al.Expression and regulation of Toll like receptors in lupus-like immune complex glomerulonephritis of MRLFas(lpr) mice[J].Nephrol Dial Transplant, 2006, 21(11):3062-
[4]Nakano S, Morimoto S, Suzuki J, el al, Role of pathogenic auto-antibody production by Toll-like receptor 9 of B cells in active systemic lupus erythematosusp.Rheumatology, 2008, 47:145-149　
[5]HOCHBERG M C.Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J].Arthritis Rheum, 1997, 40(0):17-25
[6]Ichikawa HT, Williams LP, Segal BM.Activation of APC s trough CD40 or Tolll-like receptor 9 overcomes tolerance and precipitates autoimmune disease[J].J Immunol, 2002, 169(5):2781-2787
[7]刘慧敏, 张瑞英, 耿静, 等.样受体在患者产生抗抗体中的作用[J].中华皮肤科杂志, 2007, 40(1):25-
[8]宋卫青, 李化会, 陈华波，等.基因多态性与山东汉族人群系统性红斑狼疮的相关性研究[J].中国实验诊断学, 2009, 9(13):1210-1212
[9]Xu CJ，Zhang WH，Pan HF，et al.Association study of a single nucleotide Polyrnorphism in the exon2 region of toll-1ike receptor9(TIR9)gene with susceptibility to systemic lupus erythematosus among Chinese[J].Mol Biol Rep, 2009, 36(8):2245-2248
[10]. Tao K．Fujii M，Tsukumo S，et a1．Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population．Ann Rheum Dis，2007, 66：905-909．
[11] Laska MJ, Troldborg A, Hansen B, et al.Polymorphisms within Toll-like receptors are associated with systemic lupus erythematous in a cohort of Danish females. Rheumatology (Oxford). 2013 Sep 24.

[1]	罗帅寒天龙海陆前进. 2022年系统性红斑狼疮研究新进展[J]. 中华皮肤科杂志, 2023, 56(3): 266-269.
[2]	林子沅庞天怡武静文靳慧. 多环芳烃在炎症性皮肤病发生发展中的作用研究进展[J]. 中华皮肤科杂志, 2023, 0(2): 20220271-e20220271.
[3]	王琪坚哲. 间充质干细胞三维培养技术及其在皮肤病治疗中的应用进展[J]. 中华皮肤科杂志, 2023, 0(2): 20230083-e20230083.
[4]	鲁楠谭兴友刘香牛李莉姚树兰. 微RNA单核苷酸多态性与慢性自发性荨麻疹发病风险的关联分析[J]. 中华皮肤科杂志, 2022, 55(9): 806-809.
[5]	中国医师协会皮肤科医师分会自身免疫病专业委员会 . 【开放获取】环孢素治疗免疫相关性皮肤病专家建议[J]. 中华皮肤科杂志, 2022, 55(6): 471-479.
[6]	刘影易秀莉叶竹标高天文朱冠男. 源于中国人转移性黑素瘤细胞株的建立及其生物学特性研究[J]. 中华皮肤科杂志, 2022, 55(5): 375-381.
[7]	罗帅寒天龙海陆前进, . 2021年系统性红斑狼疮研究新进展[J]. 中华皮肤科杂志, 2022, 55(4): 369-372.
[8]	中国医师协会皮肤科医师分会自身免疫性疾病学组. 环磷酰胺治疗自身免疫性皮肤病中国专家共识[J]. 中华皮肤科杂志, 2021, 54(9): 765-770.
[9]	刘军麟王薇曹智睿刘琨万多艳吴智明罗杨肖传柳刘璐殷梅. 基于靶基因捕获测序法对海南省汉族寻常型银屑病与维生素D受体基因关系的研究[J]. 中华皮肤科杂志, 2021, 54(7): 597-604.
[10]	梁高澎宋志强. 免疫球蛋白E型自身抗体在自身免疫相关皮肤病中的研究进展[J]. 中华皮肤科杂志, 2021, 54(6): 553-556.
[11]	杨晶晶赵阳樊建勇杨慧兰. rs2430561位点单核苷酸多态性与带状疱疹的易感相关性研究[J]. 中华皮肤科杂志, 2021, 54(6): 510-513.
[12]	罗帅寒天龙海陆前进. 2020年系统性红斑狼疮研究新进展[J]. 中华皮肤科杂志, 2021, 54(6): 542-545.
[13]	丁文媛孙志强黄艳平李欣郭燕张雪丽吕新翔韩建文. 内蒙古蒙古族和汉族人群白细胞介素12通路相关基因多态性与寻常型银屑病相关性及与HLA-Cw*0602交互作用研究[J]. 中华皮肤科杂志, 2021, 54(5): 414-420.
[14]	罗帅寒天龙海张桂英陆前进. 2019年系统性红斑狼疮研究新进展[J]. 中华皮肤科杂志, 2021, 54(2): 183-186.
[15]	中国医师协会皮肤科医师分会自身免疫病专业委员会. 硫唑嘌呤治疗免疫相关性皮肤病专家建议[J]. 中华皮肤科杂志, 2021, 54(2): 116-121.