| Objective:To investigate the gene polymorphisms of IRGM gene susceptibile to tuberculosis in Chinese population.Methods:A case-control study consisting of477cases with tuberculosis and483ethnically matched controls was conducted amongst a Chinese population in two Two-stages of testing. Nine SNPs (rsl3361189, rs73282255, rs4958846, rs10051924, rs7255865, rs9637876, rs72553867, rs10065172, rs4958847) in IRGM gene were analyzed. All the SNPs were detected by SNaPshot SNP typing. SNPstats software and haploview software were used to analyze gene and genotype frequencies, the deviation from Hardy-Weinberg equilibrium, haplotype frequencies and then to compare their difference between cases and controls. Based on the logistic regression method, five inheritance models (codominant, dominant, recessive, overdominant, log-additive) was analyzed for all the SNPs. Furthermore, the expression of fluorescent reporter gene, cell transfection, sub-cellular localization and western-blot analysis were used to investigate its mechanism about susceptible SNP of IRGM gene to tuberculosis.Results:(1) For IRGM gene, rs13361189was strongly associated with tuberculosis. Per allele ORs was1.52(95%CI:1.14-2.03; P=0.0038)(its best genetic model is dominant model). The results showed that subjects carrying the haplotype (rsl3361189/rs4958847/rs72553867) C-G-C had a12.76-fold higher risk of tuberculosis in the studied population (95%CI:3.08-52.95;P=5e-04).(2) Further function analysis for rs72553867(A/C) sites showed that IRGM-AA and IRGM-CC were located both in mitochondria and lysosomes of the cell. LC3positive points of IRGM-AA were3.5point/cell and significantly greater than that of IRGM-CC (2.0point/cell)(P=0.011). LC3II/GAPDH of IRGM-AA was greater than that of IRGM-CC (P=0.044). These results indicated that rs72553867(A/C) may be potential function site in the IRGM gene.Conclusion:Our results implied that some susceptibility locus for tuberculosis lied in the IRGM gene. |
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