重庆汉族儿童单核细胞趋化蛋白1基因多态性及表达水平与结核病易感性的关系

Monocyte chemotactic protein-1 gene polymorphism and monocyte chemotactic protein-1 expression in Chongqing Han children with tuberculosis

目的分析趋化因子单核细胞趋化蛋白1（MCP-1）启动子区2518基因型频率和等位基因在重庆地区汉族儿童结核病中的分布特点，探讨MCP-1基因启动子区2518A／G多态性、血清MCP-1蛋白表达水平与结核病的相关关系。方法研究对象为100例儿童结核病、100例成人结核病以及相应的200例健康对照。序列特异性引物PCR（PCR—SSP）技术检测MCP-1基因启动子区2518A／G多态性。ELISA方法测定相应不同基因型患者和对照血清MCP-1水平。结果（1）总体结核病组2518位点G等位基因频率为58％，明显高于相应的健康对照组（36％）（P〈0．01）；（2）总体结核病组2518GG基因型频率为65％，明显高于相应的健康对照组（27％）（P〈0．01）；（3）MCP-1基因启动子区2518位点GG基因型结核病患病危险性（OR=6，95％CI=3．3～11．0）高于AA基因型（OR=1．0，95％CI=0．243～1．554），且儿童GG基因型患病的危险性（OR=7，95％CI=3．0～16．6）高于成人GG基因型（OR=5．1，95％C1=2．2～12．0）；（4）2518GG基因型的MCP-1水平（124μL／L）高于AA基因型（23．10μg／L）和AG基因型（39．96恤g／L），三组比较差异有统计学意义（P〈0．01）。结核组高于正常组，儿童组高于成人组。结论在中国重庆地区汉族人中，MCP-1-2518位GG基因型作为结核病可能的危险因素，在儿童结核病的发病中具有较成人更重要的意义。

Objective The aims of this study were to evaluate whether the presence of -2518A/G polymorphism in the distal regulatory region of the monocyte chemotactic protein-1 （ MCP-1 ） was associated with tuberculosis （TB） in Chongqing Han population and to find whether it has a significant impact on the pediatric patient. Method One hundred children [ ≤ 15 years old, mean age （7.3 ± 4. 6 ） years, 53 male, 47 female] and one hundred adults [51 male, 49 female, age （44. 6± 13.5） years with TB] and 200 healthy controls of comparable age were screened for genotype by PCR-sequence-spceific primer （SSP） method. MCP-1 levels in the sera were detected by ELISA. Result （ 1 ） TB patients and controls showed different single nucleotide polymorphism （SNP） distribution patterns （58%, 36% ）. MCP-1 alleles -2518G was associated with increased TB susceptibility （P 〈 0. 01 ）. （2） The -2518 GG genotypes was associated with increased TB susceptibility （32% in TB patients and 13% in non-TB controls respectively, P 〈 0. 01 ）. （3） The odds of developing TB in genotypes GG were higher than those in homozygous AA, and the risk was higher in children than in adult （7. 0-fold in children and 5.1-fold in adults, respectively）. （4） Cases of homozygous GG had the highest plasma levels of MCP-1, which increased the likelihood of developing TB. Furthermore, higher levels were observed in children than in adults. Conclusion These findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which increases the risk of active TB infection in Chongqing Han people. These findings are more significant in child patients than in adult patients with TB.