深圳市汉族人群转化生长因子β1基因位点多态性与结核病的相关性研究

Study on the correlation between the gene polymorphisms of transforming growth factor beta-1 with tuberculosis in the Han population in Shenzhen

目的检测深圳市汉族人群TGFβ1基因rs4803455位点单核苷酸多态性(SNP)的基因类型,探讨其基因多态性与不同临床表现的结核病之间的关系。方法采用基于TaqMan探针技术的实时荧光PCR法,检测373例结核病患者(结核组)和350名健康人(对照组)TGFβ1基因rs4803455位点的等位基因型并分层分析,然后观察结核组中有病理学或者细菌学证据的肺结核患者(肺结核组)和结核性胸膜炎患者(结核性胸膜炎组)等位基因频率差异。结果rs4803455位点等位基因C/A频率在结核组373例A为31.8%(237/746),C为68.2%(509/746);对照组350名A为40.6%(284/700),C为59.4%(416/700);两组间差异有统计学意义(χ2=12.139,OR=1.466,95%CI=1.182～1.819,P=0.000)。年龄≤25岁的结核组121例A为33.5%(81/242),C为66.5%(161/242);对照组111名A为41.0%(91/222),C为59.0%(131/222);两组间差异无统计学意义(χ2=2.807,OR=1.381,95%CI=0.946～2.015,P=0.094)。年龄>25岁的结核组252例,A为31.0%(156/504),C为69.0%(348/504);对照组239名,A为40.4%(193/478),C为59.6%(285/478);两组间差异有统计学意义(χ2=9.511,OR=1.511,95%CI=1.162～1.965,P=0.002)。有病理学或者细菌学证据的肺结核组111例,A为32.4%(72/222),C为67.6%(150/222);结核性胸膜炎组57例,A为21.1%(24/114),C为78.9%(90/114);对照组350名A为40.6%(284/700),C为59.4%(416/700);前两组分别与对照组比较,差异均有统计学意义(χ2值分别为4.710、15.879,OR值分别为1.422、2.560,95%CI分别为1.034～1.957、1.592～4.116,P值均<0.05)。等位基因C在肺结核组中的频率[78.9%(90/114)]比在结核性胸膜炎组中的频率[67.6%(150/222)]高。结论TGFβ1基因rs4803455位点的基因多态性和结核病特别是结核性胸膜炎有关,等位基因C可作为预测结核病特别是结核性胸膜炎的危险因素,其中在年龄>25岁的患者中预测作用更大。

Objective To explore the single nucleotide polymorphisms（SNP）of rs4803455 from TGFβ1 gene in the Han population in Shenzhen, and study the correlation between its gene polymorphisms and different clinical manifestations of tuberculosis （TB）. Methods The allele genotypes of TGFl]l（rs4803455）in 373 TB patients （TB group） and 350 healthy controls （control group） were detected by using the real-time fluorescent PCR method based on TaqMan probe technology and performed stratified analyses. Then we observed the difference of allele frequency between in pulmonary TB patients （pulmonary TB group） and in the patients with tuberculous pleurisy （tuberculous pleurisy group）, all of which were confirmed by bacteriological and pathological examination. Results The fre- quencies of allele C/A in the genetic locus rs4803455 were as follow： allele A and allele C in TB group were 31.8% （237/746）and 68. 2%（509/746）respectively, and in control group were 40.6%/00 （284/700）and 59.4% （416/700） re- spectively. There were statistical differences between two groups （P： 0. 000,χ^2： 12. 139,OR= 1. 466, 95%CI=1. 182--1. 819）. There were not significant differences between the population aged ≤5 years of two groups （P= 0. 094, χ^2 =2. 807,OR=1. 381, 95%CI=0. 946--2. 015）： allele A and allele C in TB group with 121 cases were 33.5 % （81/242） and 66. 5 % （161/242） respectively, and in control group with 111 people were 41.0 %（91/222） and 59.0%/00（131/222） respectively. There were significant differences between the population aged ）25 years of two groups （P=0. 002,χ^2 =9. 511, OR=I. 511, 95%CI=1. 162--1. 965） ： allele A and allele C in TB group with 252 cases were 31.0% （156/504）and 69.0% （348/504）, and in control group with 239 people were 40.4%（193/478） and 59.6% （285/478）allele A and allele C in pulmonary TB group with 111 cases were 32.4%（72/222） and 67.6% （150/222）respectively, in tuberculous pleurisy group with 57 cases were 21.1%（24/114） and 78.9% （90/114） respectively, and in control group with 350 people were 40. 6%（284/700）and 59.4% （416/700）respectively, there were significant differences between pulmonary TB group or tuberculous pleurisy group and control group （P〈0.05; OR value were 1.49,2, 2. 560; 95%CI were 1. 034-1. 957, 1. 592-4. 116）. The frequency of allele C in tuberculous pleurisy group （78.9%, 90/114） was higher than that in pulmonary TB group（67.6%, 150/222）. Conclusion The gene polymorphisms of TGFβ1 （rs4803455） may be associated with TB, especially tuberculous pleurisy. Allele C may be a risk factor for prediction of TB in particular tuberculous pleurisy, and its prediction in the age of 〉25 years had greater possibility.