Study Of The Relationship Between MIF Level, MIF Gene Polymorphism And Tuberculosis

Background and ObjectiveThe macrophage migration inhibitory factor （MIF） is apro-inflammatory cytokine which plays an important role in thepathogenesis of immune diseases. In vitro, study confirms that theautocrine activity of MIF plays an important role in inhibiting the growthof virulent mycobacteria. MT mainly infects macrophages in vivo. MIF caninhibit the migration of macrophage, and promote the aggregation, invasion,proliferation, activation, and secretion of several cytokines of themacrophage at the site of infection to produce a strong immune response.Thus, MIF plays an important role in the incidence and development oftuberculosis. In this case-control study, the serum MIF level in bothtuberculosis patients and healthy controls are analyzed, and the potentialrelationship between promoter polymorphism of MIF-173G/C,-794CATT_5-8and susceptibility of tuberculosis in Southwest China.Methods（1） The peripheral blood of all the TB patients and healthy controlswere collected. Then the blood serum wad separated and stored at-20℃for testing. Genomic DNA was extracted from all the participants.（2） The serum MIF levels of TB patients and healthy controls weredetected by ELISA. And the difference of the level in two groups iscompared.（3） The MIF-173G/C polymorphism was genotyped by usingpolymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）. The genotype and allele frequencies of MIF-173in TBpatients and controls were calculated. And the relationship betweenMIF-173G/C polymorphism and susceptibility of tuberculosis in SouthwestChina was analyzed.（4） The MIF-794CATT_5-8microsatellite polymorphism of TB patientsand healthy controls was evaluated by DNA sequencing. The genotype andallele frequencies of MIF-794in TB patients and controls were calculated,and the relationship between MIF-794CATT_5-8microsatellitepolymorphism and susceptibility of tuberculosis in Southwest China wasanalyzed.Results（1） In tuberculosis group, the serum MIF level was （705.21±67.98）pg/ml, which was about2times higher than that of the control group（355.31+57.29） pg/ml （P<0.01）.（2） In tuberculosis group, the genotype frequencies of G/Ghomozygotes, G/C heterozygous and C/C homozygotes at-173site of MIF gene were50.7%,34.4%,14.9%, and G, C allele frequencies were67.9%,32.1%, respectively. In healthy controls, the genotype frequencies of G/Ghomozygotes, G/C heterozygous and C/C homozygotes at-173site of MIFgene were68.8%,24.9%,6.5%, and G, C allele frequencies were81.0%,19.0%, respectively. The genotype and allele frequencies were significantlydifferent in the two groups （P<0.01）.（3） In tuberculosis group, the frequencies of MIF-794CATT_5-8genotype were5/5（7.9%）,5/6（13.5%）,5/7（10.7%）,5/8（1.4%）,6/6（21.9%）,6/7（24.7%）,6/8（0.5%）,7/7（10.7%）,7/8（8.8%）, respectively.While in healthy controls, the frequencies were5/5（12.7%）,5/6（18.8%），5/7（13.1%）,5/8（0.8%）,6/6（23.3%）,6/7（24.9%）,7/7（3.7%）, and7/8（2.8%）, respectively. The frequencies of the allele CATT₅, CATT₆, CATT₇,CATT₈in tuberculosis group were20.7%,41.2%,32.8%,5.3%,respectively, which in healthy controls were29.0%,45.1%,24.1%,1.8%,respectively. Both the frequencies of genotype CATT₇/7, CATT₇/8and theallele CATT₇,CATT₈were significantly different in the two groups（P<0.01）.Conclusion（1） The serum MIF level in tuberculosis group is higher than that ofthe control group, which indicates that MIF is involved in the incidence anddevelopment of TB.（2） The promoter polymorphism of MIF-173may be associated with the susceptibility of tuberculosis in Southwest China. The allele MIF-173Cmay be one of the factors in increasing the risk of TB infection.（3） The promoter microsatellite polymorphism of MIF-794may beassociated with the susceptibility of tuberculosis in Southwest China. Theallele MIF-794CATT₇and CATT₈also may be the factors in increasingthe risk of TB infection.4MIF plays an important role in the incidence and development of TB inSouthwest China.