Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis

BMC Infectious Diseases volume 15, Article number: 151 (2015) Cite this article

Abstract

Background

Mannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB).

Method

A total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions.

Results

Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P < 0.05, OR 1.393, 1.302 and 1.426 respectively). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was 0.897 (95% CI: 0.282, 1.513) and 1.142 (95% CI: 0.755, 1.530) respectively (P < 0.05).

Conclusion

Polymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with the susceptibility of TB, and there were gene-gene interactions among them.

Peer Review reports

Background

Tuberculosis (TB) is a global public health issue posing serious harm to human health. China has the second highest TB burden in the world. According to the fifth TB epidemiological sampling survey in China in 2010 [1], TB prevalence in China was 459/100,000 among people aged 15 years or older. It has been estimated that [2] one-third of the world’s population is infected with tubercle bacilli whilst only 10% of people infected with Mycobacterium tuberculosis become TB patients, indicating remarkable individual differences which may be related to nutrition, constitution [3], specific and non-specific resistance [4,5] and genetic susceptibility [6,7].

According to research findings, after the pathogenic microorganism invades the body, mannose-binding lectin (MBL) binds with mannan residues on its surface, and activate MBL-associated serine Proteases (MASPs) and the lectin pathway of the complement system, generating non-specific immune responses [8,9]. Protein MASP-2 and MAp19 encoded by MASP-2 genes both can bind with MBL, generate MBL-MASP compound, and then activate C4-C9 components in the complement system, generating membrane attack complex and opsonin as well as other inflammatory cytokines promoting the killing of pathogenic microorganisms [10,11].

Previous studies suggest that polymorphisms of MBL genes in the promoter region and structural region affect the formation of MBL multimer and serum MBL concentration. The reduction of MBL multimer results in the impaired binding with ligand and the increased likelihood of being degraded by metalloproteinase [12-14]. MASP-2 gene mutation also facilitates the changes in the serum concentration of the proteins it encodes (namely, MASP2 and Map19), and results in the impaired binding with MBL and ficolin molecules, consequently blocking activation of the lectin-complement pathway resulting in impaired functioning of the non-specific body immune system [15,16].

The impact of MBL gene polymorphism on susceptibility to TB has been reported in different regions and among different races [17-19], though the findings are inconsistent between studies. Liu W and colleagues conducted analysis of the six polymorphic sites (A/B, A/C, A/D, H/L, Y/X and P/Q) of MBL genes in the Chinese Han population (including 152 male TB patients and 293 healthy males as controls), and found that only the site H/L was associated with susceptibility to TB [20]. Contrary to this, SHI J and colleagues reported that A/B was associated with susceptibility to TB in the Han population, whilst P/Q was not [21]. Further to these inconsistencies, Soborg and Selvaraj reported that low serum MBL levels could reduce tubercle bacilli infections [18,19], whilst other studies found that high of serum MBL levels [22,23] could reduce tubercle bacilli infections. Although studies have shown that Promoter -221(Y/X) mutation (YX, XX) [22] and HYB haplotype [23] could lead to decreased serum MBL [12,24] and enhanced susceptibility to TB. Liu Wei and colleagues reported that [20] the promoter -221(Y/X) mutation in the Han population was not associated with susceptibility to TB. No statistically significant difference was observed possibly due to the small sample size, and therefore the need for large sample sizes to explore the association between Y/X (rs7096206) and the susceptibility to TB in the Han population. The polymorphism of MASP-2 genes was also found to be associated with serum protein levels [15,25,26] and susceptibility to multiple diseases [27-29]. If rs2273346 (p.V377A) mutation (TC, CC) can lead to decreased serum MASP-2 concentration, is the mutation associated with susceptibility to TB? The site of rs6695096 is located at intron 7 and it is not clear that the polymorphism of this locus is associated with the susceptibility to TB. This case-control study explores the polymorphism of the rs7096206 of MBL and the rs2273346 and rs6695096 of MASP2 genes in the Han population in Hunan Province, China, as well as their gene-gene interactions, in order to determine their impact on the susceptibility to TB.

Methods

Ethical issues

The study protocol was approved by Ethical Review Committee of the Central South University Ethics Review Committee (XYSM HSP#: 2007122002A). All subjects enrolled in this study were over 19 years old and so parental consent was not required. Written informed consent was obtained from all subjects according to guidelines from the ethical review committee.

Sources of cases

Stratified sampling method was used to randomly select four county-level CDCs (i.e. Qidong County CDC, Yueyanglou District CDC, Yueyang County CDC and Hongjiang City CDC) from a total of 122 in Hunan Province. This was followed by the random selection of new TB cases registered by the four CDCs in 2009. All cases were TB patients confirmed with the TB diagnosis criteria [30] developed by Chinese Ministry of Health.

Sources of healthy controls

Stratified sampling method was used to randomly select one community health service center (i.e. Xingang Community Health Service Center) from 14 in the Kaifu district in Changsha city. This was followed by the random selection of one community (Xin’ansi) from six communities covered by the Xingang Community Health Center. Because the ratio of male to female TB patients was about 2.5:1 in Hunan [31], the healthy controls were selected from permanent residents in Xin’ansi Community by a gender-age frequency matching method. All healthy controls were confirmed with a history of contact with Mycobacterium Tuberculosis. For healthy controls with BCG scar, the average diameter of PPD (purified protein derivative) induration was ≥10 mm whilst for those without BCG scar and no history of BCG vaccination, the average diameter of PPD induration was ≥5 mm. No abnormalities were found in their chest X-rays.

Both cases and controls were selected from closed Han populations within Hunan province, minority individuals have been excluded in this research.

Estimation of sample size

Sample size estimation was based on an estimated rs6695096 frequency of 14%; OR = 1.8, α = 0.05 (paired) and β = 0.10. Based on the above assumptions, 419 subjects were to be selected as cases and healthy controls.

Information and sample collection

After each subject signed the written informed consent form, a self-administered questionnaire was used to collect demographic and selected information, which included sex, age, marital status, educational background, BMI, smoking status, alcohol drinking, tea drinking, and exposure to kitchen fumes.

5 ml of venous blood from each participant was aseptically collected in EDTA anticoagulant tubes and stored in a 4°C refrigerator before use. A blood DNA kit provided by Shanghai Sangon Biotech Co., Ltd. was then used to extract peripheral white blood cell genome.

Genotyping

In this study, PCR-SSP technology was used to sequence to genotype the rs7096206 of MBL genes and the rs2273346 and rs6695096 of MASP-2 genes. The site sequence of rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was identified in the Gene bank, and appropriate primers were designed by using Primer Premer5.0, the specificity of which was verified by using Blast software of NCBI. All the primers were produced by Shanghai Sangon Biotech Co., Ltd (Table 1). The PCR reaction system was 20 ul, including 10 ul mixture, 0.8 ul gDNA (10 ng/ul), 0.4 ul upstream primers, 0.4ul downstream primers, and 8.4 ul ddH2O. The reaction condition was 94°C, 3 min for 40 cycles (94°C for 30 sec, 58°C for 30 sec, and 72°C for 60 sec), and 72°C extension for 5 min.

Table 1 Primers site sequence of MBL and MASP-2 genes
Full size table

The enzyme digestion reaction system was 10 ul, including 2 ul PCR product, 1 ul 10X buffer, 0.5 ul corresponding restriction endonuclease, and 6.5 ul ddH2O. It was kept at 37°C over night. 5 ul enzyme-digested product was applied to 3% agarose gel (containing 0.5 ug/ml ethidium bromide). Electrolytic buffer solution: 0.5xTBE solution; voltage for sample application: 120 V; electrophoresis: 40 min. Gel imaging processing system was used to observe the electrophoresis results, determine the genotype, and take photos.

Statistical analysis

Epidata3.0 was used to input data, and SAS9.2 was used to analyze the data. χ2 test was conducted for the comparison of grouped data and Hardy-Weinberg equilibrium detection. Linkage disequilibrium analysis was evaluated by SHEsis online software (http://analysis.bio-x.cn/myAnalysis.php). The risk associated with individual alleles was calculated as the odds ratio with 95% confidence interval. To exclude possible confounding risk factors, the occurrence of TB was used as the dependent variable, rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes were used as the independent variables, and the sex, age, marital status, educational background, BMI, smoking status, alcohol drinking, tea drinking, and exposure to kitchen fumes were used as the covariates, and multivariate unconditional logistic regression analysis conducted. Marginal Structural Linear Odds Models [32] were used for point estimation and interval estimation of the relative excess risk of interaction (RERI). RERI > 0 suggests positive interactions.

Results

The study participants include 503 TB patients and 419 healthy controls. The TB patient group and the healthy control group exhibited no statistical significance difference (P > 0.05) in terms of sex, age, education background and alcohol drinking. Differences in marital status, BMI, tea drinking, smoking status, history of BCG vaccination and exposure to kitchen fumes was statistically significant (P < 0.05).

The univariate analysis showed that genotype GC at rs7096206 and genotype TC at rs6695096 were closely associated with TB incidence (OR reaching 1.338 and 1.468, respectively). Multivariate unconditional logistic regression analysis showed that rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes were associated with susceptibility to TB. Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than those in the healthy control group (P < 0.05), with OR 1.393, 1.302 and 1.426 respectively (Table 2). Linkage disequilibrium analysis showed linkage equilibrium for rs2273346 and rs6695096 of MASP-2 genes (For controls, D’ = 0.029, r2 = 0.01; for cases, D’ = 0.013, r2 = 0.00).

Table 2 MBL and MASP-2 gene polymorphism versus TB incidence
Full size table

Marginal Structural Linear Odds Models were used to analyze the impact of the interactions between MBL genes and MASP-2 genes on susceptibility to TB. Adjusting for the covariates of sex, age, marital status, educational background, BMI, smoking status, alcohol drinking, tea drinking, history of BCG vaccination, and exposure to kitchen fumes, the relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was found to be 0.897(95% CI: 0.282,1.513) and 1.142(95% CI: 0.755,1.530) respectively (P < 0.05), which suggests positive interactions (Tables 3 and 4).

Table 3 Impact of interactions between rs7096206 and rs2273346 on incidence of TB
Full size table
Table 4 Impact of interactions between rs7096206 and rs6695096 on incidence of TB
Full size table

Discussion

The incidence of TB is a result of the interactions between Mycobacterium tuberculosis and hosts. TB infection and subsequent incidence are affected by many factors, including the odds of exposure to Mycobacterium tuberculosis, toxicity of pathogenic bacteria, and the immune function of the host. Previous studies on incidence of TB primarily focused on the tubercle bacilli and impact of environmental risk factors. Over the past years, the impact of host susceptibility genes on disease has been increasingly recognized along with the development of genetic epidemiology.

Recent studies on the association between MBL genes and TB have produced different and even contradictory results. Some studies indicated that the mutation of promoter and exon 1 in MBL genes may lead to the decline of serum MBL level, while a lower serum MBL level can reduce tubercle bacilli infections [18,19]. Some other studies indicated that higher serum MBL levels can reduce tubercle bacilli infections, while higher serum MBL levels are associated with wild-type MBL genes [22,33]. Meta-analysis [34] by Denholm and colleagues indicates that polymorphism of MBL genes may be associated with serum MBL level rather than susceptibility to TB. These studies ignored the interactions between genes, as well as certain genetic and environmental factors in the analysis of gene and susceptibility to TB. Moreover, small sample sizes cannot detect real association between MBL genes and TB. Our study included some possible covariates in the logistic regression model for analyzing the relationships between MBL genes and TB, such as sex, age, marital status, educational background, BMI, smoking status, alcohol drinking, tea drinking, BCG vaccination and exposure to kitchen fumes, excluding possible confounding caused by these factors. In this way, our study results are closer to the real situation.

Our study revealed that the promoter -221(Y/X, rs7096206) mutation of the MBL genes is associated with susceptibility to TB, and the TB risk of heterozygote GC(YX) is higher than that of wild-type homozygous CC(YY) (OR = 1.393, P < 0.05), which are consistent with the findings of a Brazilian study [22]. MBL genes are associated with the serum MBL level, and promoter -221(Y/X) mutation (YX, XX) can lead to decreased serum MBL [12,24] and consequently increased susceptibility to TB.

To our knowledge, reports have been made on the association of MASP-2 genes on other disease conditions but not TB. According to Boldt and colleagues [27], p.D371Y and p.V377A (TC, CC) mutation are associated with the serum MASP-2 level in Chagas patients; Sorensen and colleagues found through twin analysis that genetic inheritance may affect the activity of MASP-2 [26]; Thiel and colleagues found that p.V377A(rs2273346) mutation (TC, CC) may lead to decreased serum MASP-2 concentration [15], and when both p.D120G and p.156_159CHNPdup undergo mutation, MASP-2 may undergo misfolding and cannot bind with MBL [16]; Yan Wang and colleagues found that the polymorphism of rs2273346 of MASP-2 genes is not associated with SARS coronavirus infections in Beijing and Guangzhou [35]; Tulio and colleagues found [29] that hepatitis C virus infection is associated with the polymorphism of MASP-2 gene p.D371Y(rs12711521) but not associated with the polymorphism of p.V377A (rs2273346). Our study reports on the association between MASP-2 gene polymorphism and TB susceptibility. The study has shown that that rs2273346 and rs6695096 of MASP-2 genes can increase susceptibility to TB, possibly because the mutation of rs2273346 (p.V377A) (TC, CC) and rs6695096 (TC, CC) can lead to decreased serum MASP-2 concentration and possibly decreased activity of MASP-2, and subsequently impairing the body immune function and increasing the risk of TB. The site of rs6695096 is located at intron7, the mutation of which may affect gene regulation and selective splicing regulation although it will not affect the sequence of amino acids [36,37] and subsequently affect serum concentration and activity of MASP-2. The biological mechanism is yet to be further examined.

Marginal Structural Linear Odds Models analysis showed that RERI between rs7096206 of MBL genes and rs2273346 of MASP-2 genes was 0.8977(95% CI:0.2821, 1.5133), and RERI between rs7096206 of MBL genes and rs6695096 was 1.1429(95% CI:0.7556,1.5301). There were significant positive interactions between rs7096206 of MBL and both rs2273346 and rs6695096 of MASP-2, which suggest that the mutations of both MBL genes and MASP-2 genes can lead to an increased risk of TB. These findings provide important reference information for studies on MBL and MASP-2 interaction mechanism.

There are some limitations to our study. First, there are six known polymorphisms within MBL-2 that affect the amounts of MBL in human plasma, but we only detected the polymorphism of rs7096206. We could therefore not analyze the impact of other polymorphisms and haplotypes of MBL gene on TB susceptibility. Secondly, we did not test for the association between rs6695096 and MASP-2, and did not find any laboratory evidence in literature to support such association. Thirdly, cases and controls in our study were sampled from different regions. However, all the participants have been limited to Han Chinese, and all the possible impacts of non-genetic factors such as sex, age, marital status, educational background, BMI, smoking status, alcohol drinking, tea drinking, and so on, were adjusted. So the results observed in our study should be reliable.

Conclusion

Polymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with TB susceptibility, and there were gene-gene interactions among them. This finding is not only significant for understanding the pathogenesis of TB, but also important for identifying populations at high risk of TB, and developing appropriate population-specific prevention measures to control the spread of TB.

References

  1. The Technical Guidance Group of the Fifth National TB Epidemiological Survey. The Fifth national tuberculosis epidemiological survey in 2010. Chin J Antituberc. 2012;34(08):485–508. in Chinese.

    Google Scholar 

  2. Ducati RG, Ruffino-Netto A, Basso LA, Santos DS. The resumption of consumption – a review on tuberculosis. Mem Inst Oswaldo Cruz. 2006;101(7):697–714.

    Article  CAS  PubMed  Google Scholar 

  3. Narasimhan P, Wood J, Macintyre CR, Mathai D. Risk factors for tuberculosis. Pulm Med. 2013;2013:828939.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Liu J, Yan J, Wan Q, Ye Q, Huang Y. The risk factors for tuberculosis in liver or kidney transplant recipients. BMC Infect Dis. 2014;14:387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rajaram MV, Ni B, Dodd CE, Schlesinger LS. Macrophage immunoregulatory pathways in tuberculosis. Semin Immunol. 2014;26(6):471–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Azad AK, Sadee W, Schlesinger LS. Innate immune gene polymorphisms in tuberculosis. Infect Immun. 2012;80(10):3343–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Guo C, Zhang H, Gao Q, He D, Tang M, Liu S, et al. Monocyte chemoattractant protein-1 in spinal tuberculosis: -362G/C genetic variant and protein levels in Chinese patients. Diagn Microbiol Infect Dis. 2014;78(1):49–52.

    Article  CAS  PubMed  Google Scholar 

  8. Turner MW. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today. 1996;17(11):532–40.

    Article  CAS  PubMed  Google Scholar 

  9. Matsushita M, Endo Y, Fujita T. Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J Immunol. 2000;164(5):2281–4.

    Article  CAS  PubMed  Google Scholar 

  10. Sato T, Endo Y, Matsushita M, Fujita T. Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein. Int Immunol. 1994;6(4):665–9.

    Article  CAS  PubMed  Google Scholar 

  11. Holmskov U, Thiel S, Jensenius JC. Collections and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol. 2003;21:547–78.

    Article  CAS  PubMed  Google Scholar 

  12. Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol. 1995;155(6):3013–20.

    CAS  PubMed  Google Scholar 

  13. Boldt AB, Petzl-Erler ML. A new strategy for mannose-binding lectin gene haplotyping. Hum Mutat. 2002;19(3):296–306.

    Article  PubMed  Google Scholar 

  14. Heitzeneder S, Seidel M, Forster-Waldl E, Heitger A. Mannan-binding lectin deficiency - Good news, bad news, doesn’t matter? Clin Immunol. 2012;143(1):22–38.

    Article  CAS  PubMed  Google Scholar 

  15. Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, et al. Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 2007;8(2):154–63.

    Article  CAS  PubMed  Google Scholar 

  16. Thiel S, Kolev M, Degn S, Steffensen R, Hansen AG, Ruseva M, et al. Polymorphisms in mannan-binding lectin (MBL)-associated serine protease 2 affect stability, binding to MBL, and enzymatic activity. J Immunol. 2009;182(5):2939–47.

    Article  CAS  PubMed  Google Scholar 

  17. Capparelli R, Iannaccone M, Palumbo D, Medaglia C, Moscariello E, Russo A, et al. Role played by human mannose-binding lectin polymorphisms in pulmonary tuberculosis. J Infect Dis. 2009;199(5):666–72.

    Article  PubMed  Google Scholar 

  18. Soborg C, Madsen HO, Andersen AB, Lillebaek T, Kok-Jensen A, Garred P. Mannose-binding lectin polymorphisms in clinical tuberculosis. J Infect Dis. 2003;188(5):777–82.

    Article  CAS  PubMed  Google Scholar 

  19. Selvaraj P, Jawahar MS, Rajeswari DN, Alagarasu K, Vidyarani M, Narayanan PR. Role of mannose binding lectin gene variants on its protein levels and macrophage phagocytosis with live Mycobacterium tuberculosis in pulmonary tuberculosis. FEMS Immunol Med Microbiol. 2006;46(3):433–7.

    Article  CAS  PubMed  Google Scholar 

  20. Liu W, Zhang F, Xin ZT, Zhao QM, Wu XM, Zhang PH, et al. Sequence variations in the MBL gene and their relationship to pulmonary tuberculosis in the Chinese Han population. Int J Tuberc Lung Dis. 2006;10(10):1098–103.

    CAS  PubMed  Google Scholar 

  21. Shi J, Xie M, Wang JM, Xu YJ, Xiong WN, Liu XS. Mannose-binding lectin two gene polymorphisms and tuberculosis susceptibility in Chinese population: a meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2013;33(2):166–71.

    Article  CAS  PubMed  Google Scholar 

  22. da Cruz HL, da Silva RC, Segat L, de Carvalho MS, Brandao LA, Guimaraes RL, et al. MBL2 gene polymorphisms and susceptibility to tuberculosis in a northeastern Brazilian population. Infect Genet Evol. 2013;19:323–9.

    Article  PubMed  Google Scholar 

  23. You HL, Lin TM, Wang JC, Li CC, Chao TL, Liao WT, et al. Mannose-binding lectin gene polymorphisms and mycobacterial lymphadenitis in young patients. Pediatr Infect Dis J. 2013;32(9):1005–9.

    Article  PubMed  Google Scholar 

  24. Vasconcelos LR, Fonseca JP, DoCarmo RF, de Mendonca TF, Pereira VR, Lucena-Silva N, et al. Mannose-binding lectin serum levels in patients with leprosy are influenced by age and MBL2 genotypes. Int J Infect Dis. 2011;15(8):e551–557.

    Article  CAS  PubMed  Google Scholar 

  25. Catarino SJ, Boldt AB, Beltrame MH, Nisihara RM, Schafranski MD, de Messias-Reason IJ. Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease. Hum Immunol. 2014;75(12):1197–202.

    Article  CAS  PubMed  Google Scholar 

  26. Sorensen GL, Petersen I, Thiel S, Fenger M, Christensen K, Kyvik KO, et al. Genetic influences on mannan-binding lectin (MBL) and mannan-binding lectin associated serine protease-2 (MASP-2) activity. Genet Epidemiol. 2007;31(1):31–41.

    Article  PubMed  Google Scholar 

  27. Boldt AB, Luz PR, Messias-Reason IJ. MASP2 haplotypes are associated with high risk of cardiomyopathy in chronic Chagas disease. Clin Immunol. 2011;140(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  28. Sorensen R, Thiel S, Jensenius JC. Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Springer Semin Immunopathol. 2005;27(3):299–319.

    Article  CAS  PubMed  Google Scholar 

  29. Tulio S, Faucz FR, Werneck RI, Olandoski M, Alexandre RB, Boldt AB, et al. MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus infection. Hum Immunol. 2011;72(10):912–5.

    Article  CAS  PubMed  Google Scholar 

  30. Ministry of Health of China. Diagnostic criteria for pulmonary tuberculosis (WS288-2008). Ministry of Health of China; 2008. Available at http://www.nhfpc.gov.cn/zwgkzt/s9491/wsbz_2.shtml

  31. Chen M, Kwaku AB, Chen Y, Huang X, Tan H, Wen SW. Gender and regional disparities of tuberculosis in Hunan, China. Int J Equity Health. 2014;13:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. VanderWeele TJ, Vansteelandt S. A weighting approach to causal effects and additive interaction in case-control studies: marginal structural linear odds models. Am J Epidemiol. 2011;174(10):1197–203.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Turner MW. The role of mannose-binding lectin in health and disease. Mol Immunol. 2003;40(7):423–9.

    Article  CAS  PubMed  Google Scholar 

  34. Denholm JT, McBryde ES, Eisen DP. Mannose-binding lectin and susceptibility to tuberculosis: a meta-analysis. Clin Exp Immunol. 2010;162(1):84–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang Y, Yan J, Shi Y, Li P, Liu C, Ma Q, et al. Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection. BMC Infect Dis. 2009;9:51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Le Hir H, Nott A, Moore MJ. How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci. 2003;28(4):215–20.

    Article  PubMed  Google Scholar 

  37. Niu DK, Yang YF. Why eukaryotic cells use introns to enhance gene expression: Splicing reduces transcription-associated mutagenesis by inhibiting topoisomerase I cutting activity. Biol Direct. 2011;6:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This investigation was supported by Fundamental Research Funds for the Central Universities of Central South University and Global Foundation for China’s Implementation Research in TB (GRANT 07-062). We thank our partners Dr Liqiong Bai (Hunan Institute of Tuberculosis Prevention and Treatment), and Jing Deng (School of Public Health, Central South University) for their input into this work.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, Hunan, 410008, PR China

    Mengshi Chen, Ying Liang, Mian Wang, Li Hu, Benjamin Kwaku Abuaku, Xin Huang, Hongzhuan Tan & Shi Wu Wen

  2. Hunan Children’s Hospital, Ziyuan RD 86, Changsha, Hunan, 410007, PR China

    Mengshi Chen

  3. School of Public Health, Xinjiang Medical University, Urumqi, Xijiang, 830054, PR China

    Ying Liang

  4. Department of Nursing, Shaoyang Medical College, Shaoyang, Hunan, 422000, PR China

    Wufei Li

  5. Beijing Center for Diseases Prevention and Control, Beijing, 100013, PR China

    Li Hu

  6. Department of Epidemiology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, PO Box LG581, Legon, Accra, Ghana

    Benjamin Kwaku Abuaku

  7. Department of Obstetrics & Gynecology, University of Ottawa, The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario, Canada

    Shi Wu Wen

Authors
  1. Mengshi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wufei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Benjamin Kwaku Abuaku
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hongzhuan Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shi Wu Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hongzhuan Tan.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

MC and HT designed the study and drafted the manuscript. MC, YL, MW, BKA, and XH carried out the data analysis. SWW supervised data analyses and results reporting. SWW, WL, BKA and LH assisted in the development of the research question and revision of the article. All authors read and approved the final manuscript.

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, M., Liang, Y., Li, W. et al. Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis. BMC Infect Dis 15, 151 (2015). https://doi.org/10.1186/s12879-015-0879-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-015-0879-y

Keywords

BMC Infectious Diseases

ISSN: 1471-2334

Contact us