Polymorphic Allele of Human MRC1 Confer Protection against Tuberculosis in a Chinese Population

Abstract

Mannose receptor is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition, and plays a critical role in shaping host immune response. Single nucleotide polymorphisms (SNPs) in the MRC1 gene may affect expression levels and differences in the structure and function of proteins in different individuals, thereby affecting individual susceptibility to pulmonary tuberculosis. However, to date, MRC1 polymorphisms associated with susceptibility to pulmonary tuberculosis have not yet been reported. The present study aimed to investigate potential associations of SNPs in the MRC1 gene with pulmonary tuberculosis in a Chinese population. Six SNPs (G1186A, G1195A, T1212C, C1221G, C1303T and C1323T) in exon 7 of the MRC1 gene were genotyped using the PCR and DNA sequencing methods in the pulmonary tuberculosis patients and the healthy controls. Linkage disequilibrium analysis was performed between polymorphic sites. The study found that the allele frequency of G1186A (rs34039386) of the MRC1 gene in a Chinese population was higher in the pulmonary tuberculosis group than the healthy control group. There was a significant difference in frequency distribution between the two groups (P = 0.037; OR = 0.76; 95% CI, 0.58-0.98). Genotypic analysis also indicated that the AG genotypes in a Chinese population were significantly correlated with pulmonary tuberculosis (P < 0.01; OR = 0.57; 95% CI, 0.37-0.87). After adjustment for age and gender, G1186A sites were found to be dominant (P < 0.01; OR = 0.59; 95% CI, 0.40-0.87), over-dominant (P = 0.045; OR = 0.69; 95% CI, 0.47-0.99) and additive models (P = 0.041; OR = 0.76; 95% CI, 0.59-0.99) in association with pulmonary tuberculosis. But, no association was found between the other 5 SNPs (G1195A, T1212C, C1221G, C1303T and C1323T) and tuberculosis (P > 0.05). This study is the first to report that genetic variants in the MRC1 gene can be associated with pulmonary tuberculosis in a Chinese population, and may reduce the risk of infecting pulmonary tuberculosis. This also provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis.

Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor

“…Needleless to say PCR has been used in host defense research and it provided valuable information in various disease settings including cirrhosis. 16,17,39,40 For instance, in a recent study the investigators demonstrated molecular evidence of bacterial antigenic material in cirrhotic ascites in the absence of a microbiological evidence for SBP. 40 MR studies, in particular, identified an association between polymorphic allele of MRC1 and susceptibility to certain infections including tuberculosis and leprosy.…”

“…40 MR studies, in particular, identified an association between polymorphic allele of MRC1 and susceptibility to certain infections including tuberculosis and leprosy. 16,17 In those studies standard PCR technique was used. This study has tested the gene encoding MR and in all patients' samples we were unable to visualize a band representative of MRC1on agarose gel electrophoresis (Figure 4a).…”

“…In a previous study the initial PCR results were not shown separately as we did in this study, instead the investigators proceeded to sequence analysis using a sophisticated sequencer. 16 According to this study's protocol the sequence analysis was meant to be dependent on obtaining positive PCR results beforehand. Since patients' results were negative we were therefore unable to undertake sequence analysis.…”

“…MRC1 gene was analyzed by standard PCR technique as previously 16 with some modification. Briefly, genomic DNA was purified as described above.…”

“…15 More recently MRC1 polymorphism has been associated with susceptibility to certain infections like tuberculosis and leprosy. 16,17 We have previously demonstrated that PMv from PCA produced vigorous respiratory burst, and we speculated that an in vivo activation state might be present. 5 Since uptake measurement of man-BSA, the MR-specific ligand, may indirectly represent MR expression we performed uptake measurement and also analyzed MRC1 gene in PCA.…”