364例蒙古族结核病患者易患基因多态性研究
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摘要
目的探讨NRAMP1、Sp110基因多态性与蒙古族人群结核病易患性的关系。方法采用病例-对照研究,选取蒙古族结核病患者180例,正常体检者184例,应用聚合酶链式反应–限制性片段长度多态性(PCR-RFLP)方法检测NRAMP1、Sp110的基因型,计算各基因型在病例组和对照组的频率,采用χ~2检验、logistic回归分析基因多态性与结核病易患性的关系。结果单因素χ~2检验发现除体质指数(BMI)外其他因素在两组中分布均衡;NRAMP1rs17235409、NRAMP1rs17235416和Sp110rs3948464位点基因多态性均与结核易患性相关,3个位点突变基因型GA+AA、TGTG/(-)+(-)/(-)、CC结核病易患的危险度分别是未突变基因型GG、TGTG/TGTG、TT的1.784、4.745和3.061倍;BMI<18.5是结核病易患的危险因素,其结核病易患的危险度是BMI≥18.5个体的4.350倍。结论 NRAMP1rs17235409、NRAMP1rs17235416和Sp110rs3948464位点基因多态性与结核病易患有关。
Objective To explore the relationship between NRAMP1, Sp110 gene polymorphism and susceptibility to tuberculosis(TB) in inner Mongolia population. Methods A case-control study was conducted, a total of 180 TB patients and184 healthy controls were selected in inner Mongolia population. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) test was performed by using blood samples to detect the genotypes, and analyze the genotype frequency distribution in the case group and the control group. The relationship between genotype and environmental factors and TB susceptibility was analyzed with χ~2 test and logistic regression. Results Single factor χ~2 analysis indicated that except body mass index(BMI) the other factors had balanced distribution between two groups, the gene polymorphisms of NRAMP1 rs17235409, NRAMP1 rs17235416 and Sp110 rs3948464 loci were associated with the susceptibility to TB,the susceptibilities of mutated genotype GA+AA, TGTG/(-)+(-)/(-), and CC to TB were 1.784, 4.745 and 3.061 times higher than those of non-mutated genotype GG, TGTG/TGTG, TT. People with BMI<18.5, a risk factors for TB, had a 4.350 times higher risk for TB compared with those with BMI≥18.5. Conclusion The gene polymorphisms of NRAMP1 rs17235409, NRAMP1 rs17235416 and Sp110 rs3948464 loci is associated with the susceptibility to TB in inner Mongolia population.
Objective To explore the relationship between NRAMP1, Sp110 gene polymorphism and susceptibility to tuberculosis(TB) in inner Mongolia population. Methods A case-control study was conducted, a total of 180 TB patients and184 healthy controls were selected in inner Mongolia population. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) test was performed by using blood samples to detect the genotypes, and analyze the genotype frequency distribution in the case group and the control group. The relationship between genotype and environmental factors and TB susceptibility was analyzed with χ~2 test and logistic regression. Results Single factor χ~2 analysis indicated that except body mass index(BMI) the other factors had balanced distribution between two groups, the gene polymorphisms of NRAMP1 rs17235409, NRAMP1 rs17235416 and Sp110 rs3948464 loci were associated with the susceptibility to TB,the susceptibilities of mutated genotype GA+AA, TGTG/(-)+(-)/(-), and CC to TB were 1.784, 4.745 and 3.061 times higher than those of non-mutated genotype GG, TGTG/TGTG, TT. People with BMI<18.5, a risk factors for TB, had a 4.350 times higher risk for TB compared with those with BMI≥18.5. Conclusion The gene polymorphisms of NRAMP1 rs17235409, NRAMP1 rs17235416 and Sp110 rs3948464 loci is associated with the susceptibility to TB in inner Mongolia population.
引文
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[7]Liu ZB,Zheng RJ,Xiao HP,et al.The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in 459 Han patients[J].Chin J Tubercul Respirat Dis,2011,34(12):923-928.
[8]Ren GX,You JT,Gong XF,et al.Sp110 and PMP22polymorphisms are associated with tuberculosis risk in a Chinese-Tibetan population[J].Oncotarget,2016,7(40):66100-66108.DOI:10.18632/oncotarget.11847.
[9]Wu F,Zhang WJ,Zhang L,et al.NRAMP1,VDR,HLA-DRB1,and HLA-DQB1 gene polymorphisms in susceptibility to tuberculosis among the Chinese Kazakh population:a case-control study[J].Biomed Res Int,2013,2013:484535.DOI:10.1155/2013/484535.
[10]王喜,任玲君,李秀玲,等.新疆维吾尔族人群HLA-DR、DQ基因多态性与结核病易感性的研究[J].中国防痨杂志,2011,33(4):197-203.Wang X,Ren LJ,Li XL,et al.A study on the correlation between the polymorphism of HLA-DR,DQ genes and the susceptibility to pulmonary tuberculosis in a Uyghur population from Xinjiang[J].Chin J Antitubercul,2011,33(4):197-203.
[11]中华人民共和国卫生部.WS 288-2008肺结核诊断标准[S].北京:人民卫生出版社,2008.Ministry of Health of the People's Republic of China.WS 288-2008 Diagnostic criteria for pulmonary tuberculosis[S].Beijing:People's Medical Publishing House,2008.
[12]Putera I,Pakasi TA,Syahmar I,et al.Effectiveness of the Bacillus Calmette-Guerin vaccine in an Indonesian population with D543NNRAMP1 polymorphism[J].J Infect Dev Ctries,2015,9(1):42-47.DOI:10.3855/jidc.5047.
[13]丛建妮,李革,周丹,等.Sp110基因多态性与重庆汉族肺结核遗传易感性关联性研究[J].卫生研究,2010,39(5):540-544.Cong JN,Li G,Zhou D,et al.Study on relation between Sp110gene polymorphism and tuberculosis genetic susceptibility of Chongqing Han People[J].J Hyg Res,2010,39(5):540-544.
[14]Medapati RV,Suvvari S,Godi S,et al.NRAMP1 and VDR gene polymorphisms in susceptibility to pulmonary tuberculosis among Andhra Pradesh population in India:a case-control study[J].BMCPulm Med,2017,17(1):89.DOI:10.1186/s12890-017-0431-5.
[15]Fernández-Mestre M,Villasmilá,Takiff H,et al.NRAMP1 and VDR gene polymorphisms in susceptibility to tuberculosis in venezuelan population[J].Dis Markers,2015,2015:860628.DOI:10.1155/2015/860628.
[16]Sahiratmadja E,Wieringa FT,van Crevel R,et al.Iron deficiency and NRAMP1 polymorphisms(INT4,D543N and 3'UTR)do not contribute to severity of anaemia in tuberculosis in the Indonesian population[J].Br J Nutr,2007,98(4):684-690.DOI:10.1017/S0007114507742691.
[17]Lei X,Zhu H,Zha L,et al.Sp110 gene polymorphisms and tuberculosis susceptibility:a systematic review and meta-analysis based on 10624 subjects[J].Infect Genet Evol,2012,12(7):1473-1480.DOI:10.1016/j.meegid.2012.05.011.
[18]罗小华,刘春颖,于彦杰,等.结核感染人群肺结核发病危险因素的研究[J].医学动物防制,2018,34(8):728-734.Luo XH,Liu CY,Yu YJ,et al.A study of risk factors of tuberculosis in tuberculosis infected population[J].J Med Pest Control,2018,34(8):728-734.
[2]Qi YC,Ma MJ,Li DJ,et al.Multidrug-resistant and extensively drug-resistant tuberculosis in multi-ethnic region,Xinjiang Uygur Autonomous Region,China[J].PLoS One,2012,7(2):e32103.DOI:10.1371/journal.pone.0032103.
[3]Oh KH,Kim HJ,Kim MH.Non-communicable diseases and risk of tuberculosis in Korea[J].Int J Tuberc Lung Dis,2016,20(7):973-977.DOI:10.5588/ijtld.15.0684.
[4]Dobler CC,Korver S,Batbayar O,et al.Multidrug-resistant tuberculosis in patients for whom first-line treatment failed,Mongolia,2010-2011[J].Emerg Infect Dis,2015,21(8):1451-1454.DOI:10.3201/eid2108.141860.
[5]Alca?s A,Van TN,Hong TV,et al.Application of genetic epidemiology to dissecting susceptibility to leprosy[J].Ann Dermatol Venereol,2005,132(1):45-47.DOI:10.1016/S0151-9638(05)79196-1.
[6]Jin DQ,Tong WJ,Yin ZG.Generalized disseminated tuberculosis in a infant which of the first symptom in the spine[J].Chin JPediat,2017,55(11):863-864.DOI:10.3760/cma.j.issn.0578-1310.2017.11.016.
[7]Liu ZB,Zheng RJ,Xiao HP,et al.The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in 459 Han patients[J].Chin J Tubercul Respirat Dis,2011,34(12):923-928.
[8]Ren GX,You JT,Gong XF,et al.Sp110 and PMP22polymorphisms are associated with tuberculosis risk in a Chinese-Tibetan population[J].Oncotarget,2016,7(40):66100-66108.DOI:10.18632/oncotarget.11847.
[9]Wu F,Zhang WJ,Zhang L,et al.NRAMP1,VDR,HLA-DRB1,and HLA-DQB1 gene polymorphisms in susceptibility to tuberculosis among the Chinese Kazakh population:a case-control study[J].Biomed Res Int,2013,2013:484535.DOI:10.1155/2013/484535.
[10]王喜,任玲君,李秀玲,等.新疆维吾尔族人群HLA-DR、DQ基因多态性与结核病易感性的研究[J].中国防痨杂志,2011,33(4):197-203.Wang X,Ren LJ,Li XL,et al.A study on the correlation between the polymorphism of HLA-DR,DQ genes and the susceptibility to pulmonary tuberculosis in a Uyghur population from Xinjiang[J].Chin J Antitubercul,2011,33(4):197-203.
[11]中华人民共和国卫生部.WS 288-2008肺结核诊断标准[S].北京:人民卫生出版社,2008.Ministry of Health of the People's Republic of China.WS 288-2008 Diagnostic criteria for pulmonary tuberculosis[S].Beijing:People's Medical Publishing House,2008.
[12]Putera I,Pakasi TA,Syahmar I,et al.Effectiveness of the Bacillus Calmette-Guerin vaccine in an Indonesian population with D543NNRAMP1 polymorphism[J].J Infect Dev Ctries,2015,9(1):42-47.DOI:10.3855/jidc.5047.
[13]丛建妮,李革,周丹,等.Sp110基因多态性与重庆汉族肺结核遗传易感性关联性研究[J].卫生研究,2010,39(5):540-544.Cong JN,Li G,Zhou D,et al.Study on relation between Sp110gene polymorphism and tuberculosis genetic susceptibility of Chongqing Han People[J].J Hyg Res,2010,39(5):540-544.
[14]Medapati RV,Suvvari S,Godi S,et al.NRAMP1 and VDR gene polymorphisms in susceptibility to pulmonary tuberculosis among Andhra Pradesh population in India:a case-control study[J].BMCPulm Med,2017,17(1):89.DOI:10.1186/s12890-017-0431-5.
[15]Fernández-Mestre M,Villasmilá,Takiff H,et al.NRAMP1 and VDR gene polymorphisms in susceptibility to tuberculosis in venezuelan population[J].Dis Markers,2015,2015:860628.DOI:10.1155/2015/860628.
[16]Sahiratmadja E,Wieringa FT,van Crevel R,et al.Iron deficiency and NRAMP1 polymorphisms(INT4,D543N and 3'UTR)do not contribute to severity of anaemia in tuberculosis in the Indonesian population[J].Br J Nutr,2007,98(4):684-690.DOI:10.1017/S0007114507742691.
[17]Lei X,Zhu H,Zha L,et al.Sp110 gene polymorphisms and tuberculosis susceptibility:a systematic review and meta-analysis based on 10624 subjects[J].Infect Genet Evol,2012,12(7):1473-1480.DOI:10.1016/j.meegid.2012.05.011.
[18]罗小华,刘春颖,于彦杰,等.结核感染人群肺结核发病危险因素的研究[J].医学动物防制,2018,34(8):728-734.Luo XH,Liu CY,Yu YJ,et al.A study of risk factors of tuberculosis in tuberculosis infected population[J].J Med Pest Control,2018,34(8):728-734.