Relationship between genetic polymorphisms of IL-10 promoter and antituberculosis drug-induced liver injury
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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。 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. -
Key words:
- IL-10 /
- Gene Polymorphism /
- Antituberculosis drug /
- Liver injury
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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) 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 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/Ca 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。 -
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