IL-10启动子区基因多态性与抗结核药物性肝损伤关系

李标; 孔化文; 李玉红; 杜莹; 崇英之; 任琦; 郑国颖; 冯福民

doi:10.16462/j.cnki.zhjbkz.2019.01.012

IL-10启动子区基因多态性与抗结核药物性肝损伤关系

doi: 10.16462/j.cnki.zhjbkz.2019.01.012

063210 唐山, 华北理工大学公共卫生学院流行病与卫生统计学系

基金项目:

国家自然科学基金 81041096

大学生创新创业训练计划项 X2016158

详细信息

通讯作者:
冯福民, E-mail: fm_feng@sina.com

中图分类号: R181.23
计量
- 文章访问数: 253
- HTML全文浏览量: 93
- PDF下载量: 19
- 被引次数: 0
出版历程
- 收稿日期: 2018-07-17
- 修回日期: 2018-10-03
- 刊出日期: 2019-01-10

Relationship between genetic polymorphisms of IL-10 promoter and antituberculosis drug-induced liver injury

Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, Tangshan 063210, China

Funds:

National Natural Science of China 81041096

College Students' Innovation and Entrepreneurship Training Program X2016158

More Information

Corresponding author: FENG Fu-min, E-mail: fm_feng@sina.com

摘要

摘要: 目的探讨白细胞介素10（interleukin 10，IL-10）启动子区的-592 A/C（rs1800872）和-819 C/T（rs1800871）位点基因多态性与抗结核药物性肝损伤（antituberculosis drug-induced liver injury，ADLI）易感性关系。方法采用病例对照研究设计，以发生肝损伤的180例患者为病例组，按性别进行频数匹配未发生肝损伤的180例患者为对照组。对研究对象进行流行病学调查，同时留取外周血以聚合酶链式反应-限制性片段长度多态性技术鉴定两位点基因型。结果研究对象两位点的基因型分布在ADLI间差异均无统计学意义（均有P>0.05）。-592 A/C位点的C等位基因在病例组的频率高于对照组，显性模型（CC+AC）出现ADLI的危险是AA型的1.62倍，分布差异均有统计学意义（均有P<0.05）。-819 C/T位点等位基因在两组中的分布差异无统计学意义（P=0.190），但-592 A/C和-819 C/T两位点间存在连锁不平衡，单倍型-819 C/-512 C（OR=1.37，95%CI：1.02~1.85）和-819 C/-512 A（OR=0.49，95%CI：0.34~0.70）在病例组和对照组中的分布均有统计学差异（均有P<0.05）。结论 IL-10启动子区-592 A/C和-819 C/T位点的基因多态性可能与ADLI易感性有关。
- 白细胞介素10 /
- 基因多态性 /
- 抗结核药物 /
- 肝损伤
Abstract: Objective To investigate the relationship between interleukin 10 (IL-10) -592 (rs1800872) and -819 (rs1800871) promoter genetic polymorphisms and the susceptibility of antituberculosis drug-induced liver injury (ADLI). Methods A case-control study was conducted. Epidemiology survey data and peripheral blood samples were obtained from the patients. Two IL-10 gene polymorphisms (-592 A/C and 819 C/T) were genotyped with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) in Chinese Han ADLI subjects (n=180) and sex matched by frequency matching in control subjects (n=180). Results No significant differences in genotypes of IL-10 -592 site and IL-10 -819 site between ADLI group and that of the control group were noticed (all P>0.05). The mutant alleles -592 C of IL-10 gene polymorphism was significantly higher in ADLI subjects compared to controls, and in dominant model, the frequency of CC+AC genotype was 1.62 higher among the cases than controls (all P<0.05). Significant difference in allele -819 C/T between the ADLI group and the control group were not found (P=0.190). The polymorphisms at -819 C/T and -592 A/C variants of IL-10 gene were found to be good linkage disequilibrium. The CC haplotype represent genetic risk factor (OR=1.37, 95% CI: 1.02-1.85) and CA haplotype represent genetic protect factor (OR=0.49, 95% CI: 0.34-0.70) for ADLI in the subjects. Conclusions The polymorphisms in IL-10 gene -592 A/C and -819 C/T are associated with ADLI.
- IL-10 /
- Gene Polymorphism /
- Antituberculosis drug /
- Liver injury

HTML全文

表 1 IL-10 -592 A/C和-819 C/T基因型和等位基因频率分布[n(%)]

Table 1. Distribution of genotype and allele frequency on IL-10 -592 A/C and -819 C/T [n(%)]

基因位点	组别	病例组	对照组	χ²值	P值
IL-10 -592 A/C	基因型
	AA	56(31.1)	76(42.2)	4.942	0.085
	AC	84(46.7)	73(40.6)
	CC	40(22.2)	31(17.2)
	等位基因
	A	196(54.4)	225(62.5)	4.810	0.028
	C	164(45.6)	135(37.5)
IL-10 -819 C/T	基因型
	CC	71(39.5)	81(45.0)	1.549	0.461
	CT	76(42.2)	73(40.6)
	TT	33(18.3)	26(14.4)
	等位基因
	C	218(60.6)	235(65.3)	1.720	0.190
	T	142(39.4)	125(34.7)

下载: 导出CSV

表 2 IL-10 -592 A/C基因多态性与ADLI相关性[n(%)]

Table 2. Association between IL-10 -592 A/C polymorphisms and ADLI [n(%)]

基因型	病例组(n=180)	对照组(n=180)	OR(95% CI)值	χ²值	P值
共显性模型
AA	56(31.1)	76(42.2)	1.00
AC	84(46.7)	73(40.6)	1.56(0.98~2.49)	3.524	0.600
CC	40(22.2)	31(17.2)	1.75(0.98~3.14)	3.586	0.058
显性模型
AA			1.00
CC+AC	124(68.9)	104(57.8)	1.62(1.05~2.49)	4.785	0.029
隐性模型
CC			1.00
AA+AC	140(77.8)	149(82.8)	0.73(0.43~1.23)	1.421	0.233

下载: 导出CSV

表 3 IL-10-592 A/C和-819 C/T两位点单倍型频率与ADLI关系(%)

Table 3. Relationship between haplotype frequency of IL-10 -592 A/C and -819 C/T and ADLI (%)

-819 C/T & -592 A/C^a	病例组	对照组	OR(95% CI)值	χ²值	P值
CC	44.9	37.5	1.37(1.02~1.85)	4.395	0.036
CA	15.6	27.8	0.49(0.34~0.70)	15.273	<0.001
TA	38.8	34.7	1.21(0.89~1.63)	1.448	0.229
注：^aTC单倍型仅出现在病例组，频率0.7%低于分析阈值3%，不进行计算。

下载: 导出CSV

参考文献(18)

[1]	赵红, 范颖, 谢雯. 抗结核药物所致肝损伤临床研究进展[J]. 现代医药卫生, 2018, 34(13): 1953-1955. DOI: 10.3969/j.issn.1009-5519.2018.13.005. Zhao H, Fan Y, Xie W. Development of liver injury caused by antituberculosis drugs[J]. J Mod Med Health, 2018, 34(13): 1953-1955. DOI: 10.3969/j.issn.1009-5519.2018.13.005.
[2]	高丽, 李世明, 史哲, 等. GSTA1/GSTM3基因多态性与抗结核药物性肝损伤的相关性分析[J]. 中华疾病控制杂志, 2014, 18(7): 585-589. doi: 10.16462/j.cnki.zhjbkz.2016.09.009 Gao L, Li SM, Shi Z, et al. Analysis of the relationship between the genetic polymorphisms of glutathione S-transferase A1, M3(GSTA1, GSTM3) and the susceptibility to antituberculosis drug-induced hepatotoxicity[J]. Chin J Dis Control Prev, 2014, 18(7): 585-589. doi: 10.16462/j.cnki.zhjbkz.2016.09.009
[3]	郭桐君, 李玉红, 朱凌妍, 等. CYP3A53和CYP3A418B基因多态性与抗结核药物性肝损伤的关系[J]. 中华疾病控制杂志, 2016, 20(9): 897-900. DOI: 10.16462/j.cnki.zhjbkz.2016.09.009. Guo TJ, Li YH, Zhu LY, et al. Association between CYP3A5* 3/CYP3A4* 18-B gene polymorphisms and liver injury induced by anti-tuberculosis drugs[J]. Chin J Dis Control Prev, 2016, 20(9): 897-900. DOI: 10.16462/j.cnki.zhjbkz.2016.09.009.
[4]	井申荣, 邹全明. 白细胞介素10的研究进展[J]. 免疫学杂志, 2006, 22(z1): 26-28. DOI: 10.13431/j.cnki.immunol.j.20060203. Jing SR, Zhou QM. Advances in interleukin 10[J]. Immunol J, 2006, 22(z1): 26-28. DOI: 10.13431/j.cnki.immunol.j.20060203.
[5]	许银姬, 佟金平, 王惠娟. IL-10基因多态性与特应性皮炎发生的相关性[J]. 基础医学与临床, 2010, 30(7): 763-766. DOI: 10.16352/j.issn.1001-6325.2010.07.032. Xu YJ, Tong JP, Wang HJ. Association of IL-10 gene polymorphism with atopic dermatitis[J]. Basic Clin Med, 2010, 30(7): 763-766. DOI: 10.16352/j.issn.1001-6325.2010.07.032.
[6]	Behniafard N, Amirzargar AA, Gharagozlou M, et al. Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-β1 in Iranian children with atopic dermatitis[J]. Allergol Immunopathol, 2018, 46(2): 155-159. DOI: 10.1016/j.aller.2017.05.007.
[7]	Shi YY, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci[J]. Cell Res, 2005, 15(2): 97-98. DOI: 10.1038/sj.cr.7290272.
[8]	Li Z, Zhang Z, He Z, et al. A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis[J]. Cell Res, 2009, 19(4): 519-523. DOI: 10.1038/cr.2009.33.
[9]	汪洁冰, 潘海峰, 叶冬青. Lnc5150基因多态性与系统性红斑狼疮的相关性研究[J]. 中华疾病控制杂志, 2018, 22(9): 929-932. DOI: 10.16462/j.cnki.zhjbkz.2018.09.014. Wang JB, Pan HF, Ye DQ. Association of lnc5150 gene polymorphisms with systemic lupus erythematosus[J]. Chin J Dis Control Prev, 2018, 22(9): 929-932. DOI: 10.16462/j.cnki.zhjbkz.2018.09.014.
[10]	Simona, Volpi, Cristina, et al. Transcriptional regulation of the pituitary vasopressin V1b receptor involves a GAGA-binding protein[J]. J Biol Chem, 2002, 277(31): 27829-27838. DOI: 10.1074/jbc.M201508200.
[11]	Matsumoto K, Oki A, Satoh T, et al. Interleukin-10-1082 gene polymorphism and susceptibility to cervical cancer among Japanese women[J]. Jap J Clin Oncol, 2010, 40(11): 1113-1119. DOI: 10.1093/jjco/hyq094.
[12]	Yu Z, Liu Q, Huang C, et al. The interleukin 10-819C/T polymorphism and cancer risk: a HuGE review and meta-analysis of 73 studies including 15, 942 cases and 22, 336 controls[J]. OMICS, 2013, 17(4): 200-214. DOI: 10.1089/omi.2012.0089.
[13]	王春青, 侯志平, 何培元, 等. 河北汉族HBV感染者血清IL-10水平及IL-10基因启动子区-819 C/T、-592 A/C多态性观察[J]. 山东医药, 2017, 57(3): 98-100. DOI: 10.3969/j.issn.1002-266X.2017.03.032. Wang CQ, Hou ZP, He PY, et al. Observation on serum il-10 level and -819 C/T and -592 A/C polymorphisms in the promoter region of IL-10 gene in HBV infection of han nationality in hebei province[J]. Shandong Med J, 2017, 57(3): 98-100. DOI: 10.3969/j.issn.1002-266X.2017.03.032.
[14]	吉顺年, 王永年, 邓新桃, 等. 健康汉族人群白细胞介素10-592A/C基因多态性及血清水平[J]. 江苏预防医学, 2015, 26(5): 8-10. DOI: 10.13668/j.issn.1006-9070.2015.05.003. Ji SN, Wang YN, Den XT, et al. Polymorphism and concentration of interleukin 10-592A/C in normal Han Chinese population[J]. Jiangsu J Prev Med, 2015, 26(5): 8-10. DOI: 10.13668/j.issn.1006-9070.2015.05.003.
[15]	朱雅婷, 魏娟, 张永军, 等. 新疆维吾尔族、汉族人群IL-10基因多态性与分泌量的相关性研究[J]. 中国免疫学杂志, 2013, 29(10): 1022-1027. DOI: 10.3969/j.issn.1000-484X.2013.10.003.Zhu YT, Wei J, Zhang YJ, et al. The study of IL-10 gene polymorphisms and contents relationship between Han and Uygur in Xinjiang[J]. Chinese Journal Immunology, 2013, 29(10): 1022-1027. DOI: 10.3969/j.issn.1000-484X.2013.10.003.
[16]	谭国超, 徐春娟, 马纪龙, 等. 我国西部汉族人IL-10基因多态性与肺结核易感性的相关性研究[J]. 中华肺部疾病杂志, 2016, 9(1): 56-59. DOI: 10.3877/cma.j.issn.1674-6902.2016.01.013. Tan GC, Xu CJ, Ma JL, et al. Association analysis of IL-10 gene polymorphisms with tuberculosis susceptibility[J]. Chin J Lung Dis, 2016, 9(1): 56-59. DOI: 10.3877/cma.j.issn.1674-6902.2016.01.013.
[17]	李美江. 白细胞介素基因多态性与桂西地区妇女乳腺癌遗传易感性研究[J]. 右江民族医学院学报, 2014, 36(3): 339-340, 343. DOI: 10.3969/j.issn.1001-5817.2014.03.007. Li MJ. The relationship between interleukin gene polymorphism and females genetic susceptibility to breast cancer in Western Guangxi[J]. J Youjiang Med Univ Nation, 2014, 36(3): 339-340, 343. DOI: 10.3969/j.issn.1001-5817.2014.03.007.
[18]	张少言, 林赟霄, 赵外荣, 等. 上海市老年高血压患者中医证型与IL-10启动子rs1800871基因多态性的相关性分析[J]. 中华中医药学刊, 2017, (3): 618-621. DOI: 10.13193/j.issn.1673-7717.2017.03.029. Zhang SY, Lin YX, Zhao WR, et al. Correlation Analysis of TCM Syndromes of Shanghai Elderly Hypertensive Patients with IL-10 Gene Polymorphisms in Promoter Region[J]. Chinese Archives Traditional Chinese Medicine, 2017, (3): 618-621. DOI: 10.13193/j.issn.1673-7717.2017.03.029.