MBL2基因P54位点多态性与结核易感性相关性的Meta分析
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摘要
目的应用Meta的分析方法探讨甘露聚糖结合凝集素2(mannose-binding lectin 2,MBL2)基因P54位点多态性与结核易感性的关系。方法用计算机检索万方、CNKI、PubMed、CBM、EMbase等数据库,查找国内外从建库至2016年5月20日公开发表的所有关于研究MBL2基因多态性与肺结核易感性关系的相关文献。由两名评价者根据其纳入与排除标准筛选文献,提取并评价文献资料,最后采用RevMan5.2软件及STATA 10.0软件进行Meta分析。结果最终共纳入21个病例对照研究,其中包括结核组4 745例,对照组5 379例,经异质性检验,各研究之间存在统计学异质性(P<0.1),故总体分析采用随机效应模型Meta分析结果显示:对于总体人群而言,MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=1.08,95%CI=0.92~1.26,P=0.35);同时,在亚洲人群中MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=1.18,95%CI=0.99~1.41,P=0.07);在高加索人群中MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=0.83,95%CI=0.63~1.09,P=0.18);在非洲人群中MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=0.80,95%CI=0.55~1.18,P=0.26)。结论 MBL2基因P54位点多态性与结核的发病风险可能不存在相关性。
Objective To elucidate the association between MBL2 gene P54 A/D polymorphism and the risk of tuberculosis through meta-analysis. Methods Databases including Embase,PubMed,CNKI and Wanfang were searched for literatures regarding domestic and international case-control studies about the associations between MBL2 gene P54 A/D polymorphism and tuberculosis risk(updated to May 20 th 2016).Literatures were assessed by two reviewers and were screened according to the inclusion and exclusion criteria,extracted data were analyzed statistically by Revman 5.2 software and Stata 10.0 software. Results A total of21 case-control studies including 4 745 cases and 5 379 controls were analyzed in this meta-analysis.The random effect model was adopted for the analysis based on the result of heterogeneity test.The analysis showed that MBL2 gene 54 A/D polymorphism was not significantly associated with the risk of TB(OR=1.08,95%CI=0.92-1.26,P=0.35)in overall population by random effect model.Stratified analysis by ethnicity revealed no significant associations between MBL2 gene 54 A/D polymorphism and TB risk were observed in Asians(OR=1.18,95%CI=0.99-1.41,P=0.07),in Caucasians(OR=0.83,95%CI=0.63-1.09,P=0.18)and in Africans(OR=0.80,95%CI=0.55-1.18,P=0.26). Conclusions The polymorphism of MBL2 gene P54 A/D is not significantly associated with tuberculosis susceptibility.
Objective To elucidate the association between MBL2 gene P54 A/D polymorphism and the risk of tuberculosis through meta-analysis. Methods Databases including Embase,PubMed,CNKI and Wanfang were searched for literatures regarding domestic and international case-control studies about the associations between MBL2 gene P54 A/D polymorphism and tuberculosis risk(updated to May 20 th 2016).Literatures were assessed by two reviewers and were screened according to the inclusion and exclusion criteria,extracted data were analyzed statistically by Revman 5.2 software and Stata 10.0 software. Results A total of21 case-control studies including 4 745 cases and 5 379 controls were analyzed in this meta-analysis.The random effect model was adopted for the analysis based on the result of heterogeneity test.The analysis showed that MBL2 gene 54 A/D polymorphism was not significantly associated with the risk of TB(OR=1.08,95%CI=0.92-1.26,P=0.35)in overall population by random effect model.Stratified analysis by ethnicity revealed no significant associations between MBL2 gene 54 A/D polymorphism and TB risk were observed in Asians(OR=1.18,95%CI=0.99-1.41,P=0.07),in Caucasians(OR=0.83,95%CI=0.63-1.09,P=0.18)and in Africans(OR=0.80,95%CI=0.55-1.18,P=0.26). Conclusions The polymorphism of MBL2 gene P54 A/D is not significantly associated with tuberculosis susceptibility.
引文
[1]李宇,吴芳,章乐,等.MBL基因多态性与新疆汉族人群结核病易感性的研究[J].中国人兽共患病学报,2011,27(9):769-773.
[2]Wu L,Deng H,Zheng Y,et al.An association study of NRAMP1,VDR,MBL and their interaction with the susceptibility to tuberculosis in a Chinese population[J].Int J Infect Dis,2015,38:129-135.
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[6]Araújo MS,Graca ES,Azevedo VN,et al.No evidence of association between MBL2A/O polymorphisms and Mycobacterium tuberculosis infection in populations from the Brazilian Amazon region[J].Hum Immunol,2013,74(1):82-84.
[7]李岩.NRAMP1及MBL SNPs与宁夏海原回族肺结核病遗传易感性的关联性研究[D].银川:宁夏医科大学,2009.
[8]Little J,Higgins JP,Ioannidis JP,et al.STrengthening the REporting of Genetic Association studies(STREGA)--an extension of the STROBE statement[J].Eur J Clin Invest,2009,39(4):247-266.
[9]Bellamy R,Ruwende C,McAdam KP,et al.Mannose binding protein deficiency is not associated with malaria,hepatitis B carriage nor tuberculosis in Africans[J].QJM,1998,91(1):13-18.
[10]Cosar H,Ozkinay F,Onay H,et al.Low levels of mannosebinding lectin confers protection against tuberculosis in Turkish children[J].Eur J Clin Microbiol Infect Dis,2008,27(12):1165-1169.
[11]de Wit E,van der Merwe L,van Helden PD,et al.Gene-gene interaction between tuberculosis candidate genes in a South African population[J].Mamm Genome,2011,22(1-2):100-110.
[12]Hijikata M,Matsushita I,Hang NT,et al.Age-dependent association of mannose-binding lectin polymorphisms with the development of pulmonary tuberculosis in Viet Nam[J].Hum Immunol,2014,75(8):840-846.
[13]Liu W,Zhang F,Xin ZT,et al.Sequence variations in the MBLgene and their relationship to pulmonary tuberculosis in the Chinese Han population[J].Int J Tuberc Lung Dis,2006,10(10):1098-1103.
[14]Ocejo-Vinyals JG,Lavín-Alconero L,Sánchez-Velasco P,et al.Mannose-binding lectin promoter polymorphisms and gene variants in pulmonary tuberculosis patients from cantabria(northern Spain)[J].Pulm Med,2012,2012:469128.
[15]Ozba-Gerceker F,Tezcan I,Berkel AI,et al.The effect of mannose-binding protein gene polymorphisms in recurrent respiratory system infections in children and lung tuberculosis[J].Turk J Pediatr,2003,45(2):95-98.
[16]Selvaraj P,Jawahar MS,Rajeswari DN,et al.Role of mannose binding lectin gene variants on its protein levels and macrophage phagocytosis with live Mycobacterium tuberculosis in pulmonary tuberculosis[J].FEMS Immunol Med Microbiol,2006,46(3):433-437.
[17]Selvaraj P,Narayanan PR,Reetha AM.Association of functional mutant homozygotes of the mannose binding protein gene with susceptibility to pulmonary tuberculosis in India[J].Tuber Lung Dis,1999,79(4):221-227.
[18]Singla N,Gupta D,Joshi A,et al.Association of mannosebinding lectin gene polymorphism with tuberculosis susceptibility and sputum conversion time[J].Int J Immunogenet,2012,39(1):10-14.
[19]Sborg C,Madsen HO,Andersen AB,et al.Mannose-binding lectin polymorphisms in clinical tuberculosis[J].J Infect Dis,2003,188(5):777-782.
[20]You HL,Lin TM,Wang JC,et al.Mannose-binding lectin gene polymorphisms and mycobacterial lymphadenitis in young patients[J].Pediatr Infect Dis J,2013,32(9):1005-1009.
[21]方桂兴,银春莲.甘露糖结合凝集素基因多态性与壮族人群肺结核易感性的关系研究[J].国际呼吸杂志,2011,31(6):428-430.
[22]周江,张万江.甘露聚糖结合凝集素基因A/B位点与新疆维吾尔族结核病的相关性研究[J].中国防痨杂志,2012,34(7):445-451.
[2]Wu L,Deng H,Zheng Y,et al.An association study of NRAMP1,VDR,MBL and their interaction with the susceptibility to tuberculosis in a Chinese population[J].Int J Infect Dis,2015,38:129-135.
[3]赵珩博,朱圭娜,陈丹丹,等.MBL基因rs1800450与宁夏人群肺结核易感性研究[J].宁夏医科大学学报,2014,36(8):889-893.
[4]冯福民,郝金奇,陈怡,等.河北唐山汉族人群VDR和MBP基因交互作用与肺结核发病的相关性[J].重庆医学,2010,39(12):1527-1529,1532.
[5]Alagarasu K,Selvaraj P,Swaminathan S,et al.Mannose binding lectin gene variants and susceptibility to tuberculosis in HIV-1infected patients of South India[J].Tuberculosis(Edinb),2007,87(6):535-543.
[6]Araújo MS,Graca ES,Azevedo VN,et al.No evidence of association between MBL2A/O polymorphisms and Mycobacterium tuberculosis infection in populations from the Brazilian Amazon region[J].Hum Immunol,2013,74(1):82-84.
[7]李岩.NRAMP1及MBL SNPs与宁夏海原回族肺结核病遗传易感性的关联性研究[D].银川:宁夏医科大学,2009.
[8]Little J,Higgins JP,Ioannidis JP,et al.STrengthening the REporting of Genetic Association studies(STREGA)--an extension of the STROBE statement[J].Eur J Clin Invest,2009,39(4):247-266.
[9]Bellamy R,Ruwende C,McAdam KP,et al.Mannose binding protein deficiency is not associated with malaria,hepatitis B carriage nor tuberculosis in Africans[J].QJM,1998,91(1):13-18.
[10]Cosar H,Ozkinay F,Onay H,et al.Low levels of mannosebinding lectin confers protection against tuberculosis in Turkish children[J].Eur J Clin Microbiol Infect Dis,2008,27(12):1165-1169.
[11]de Wit E,van der Merwe L,van Helden PD,et al.Gene-gene interaction between tuberculosis candidate genes in a South African population[J].Mamm Genome,2011,22(1-2):100-110.
[12]Hijikata M,Matsushita I,Hang NT,et al.Age-dependent association of mannose-binding lectin polymorphisms with the development of pulmonary tuberculosis in Viet Nam[J].Hum Immunol,2014,75(8):840-846.
[13]Liu W,Zhang F,Xin ZT,et al.Sequence variations in the MBLgene and their relationship to pulmonary tuberculosis in the Chinese Han population[J].Int J Tuberc Lung Dis,2006,10(10):1098-1103.
[14]Ocejo-Vinyals JG,Lavín-Alconero L,Sánchez-Velasco P,et al.Mannose-binding lectin promoter polymorphisms and gene variants in pulmonary tuberculosis patients from cantabria(northern Spain)[J].Pulm Med,2012,2012:469128.
[15]Ozba-Gerceker F,Tezcan I,Berkel AI,et al.The effect of mannose-binding protein gene polymorphisms in recurrent respiratory system infections in children and lung tuberculosis[J].Turk J Pediatr,2003,45(2):95-98.
[16]Selvaraj P,Jawahar MS,Rajeswari DN,et al.Role of mannose binding lectin gene variants on its protein levels and macrophage phagocytosis with live Mycobacterium tuberculosis in pulmonary tuberculosis[J].FEMS Immunol Med Microbiol,2006,46(3):433-437.
[17]Selvaraj P,Narayanan PR,Reetha AM.Association of functional mutant homozygotes of the mannose binding protein gene with susceptibility to pulmonary tuberculosis in India[J].Tuber Lung Dis,1999,79(4):221-227.
[18]Singla N,Gupta D,Joshi A,et al.Association of mannosebinding lectin gene polymorphism with tuberculosis susceptibility and sputum conversion time[J].Int J Immunogenet,2012,39(1):10-14.
[19]Sborg C,Madsen HO,Andersen AB,et al.Mannose-binding lectin polymorphisms in clinical tuberculosis[J].J Infect Dis,2003,188(5):777-782.
[20]You HL,Lin TM,Wang JC,et al.Mannose-binding lectin gene polymorphisms and mycobacterial lymphadenitis in young patients[J].Pediatr Infect Dis J,2013,32(9):1005-1009.
[21]方桂兴,银春莲.甘露糖结合凝集素基因多态性与壮族人群肺结核易感性的关系研究[J].国际呼吸杂志,2011,31(6):428-430.
[22]周江,张万江.甘露聚糖结合凝集素基因A/B位点与新疆维吾尔族结核病的相关性研究[J].中国防痨杂志,2012,34(7):445-451.