Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and chronic gastritis

Abstract

Abstract. Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify associations of the functional polymorphisms of the MIF gene promoter with the development of chronic gastritis. The study was performed with 290 stocked DNAs from subjects with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Both the 7/7-CATT repeat at position -794 and the -173 C/C genotypes were significantly associated with a risk of developing severe gastric mucosal atrophy (OR, 9.69; 95% CI, 1.29-72.5; and OR, 4.60; 95% CI, 1.05-20.2, respectively). In subjects younger than 60 years old, the number of 7-CATT alleles was significantly correlated with both the activity and inflammation scores (p=0.0079 and 0.0080, respectively). Our results suggested that functional promoter polymorphisms of the MIF gene might be associated with the severity of gastric mucosal inflammation in younger subjects and with the subsequent development of mucosal atrophy.

Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa

“…Important roles of both IL-17 and MIF in the inflammatory response to H. pylori infection have been demonstrated (25,26). Recently, we have also shown the potential roles of IL-17A, -17F and MIF polymorphisms in the gastric inflammation (27,28) and carcinogenesis (29,30).…”

“…and H. pylori related chronic gastritis (27). Since the important roles that MIF plays with respect to gastric inflammation and carcinogenesis, it seems reasonable to expect that MIF gene promoter functional polymorphisms is also associated with CIHM status in the gastric mucosa.…”

“…Polymorphism was genotyped by PCR-SSCP method as previously described (27)(28)(29)(30). To detect the IL-17A and -17F polymorphisms, using the primer pairs (IL-17AF, 5'-aacaagtaagaatgaaaagagg acatggt-3'; IL-17AR, 5'-cccccaatgaggtcatagaagaatc-3'; IL-17FF, 5'-gtg taggaacttgggctgcatcaat-3'; and IL-17FR: 5'-agtggatat gcacctcttactgcaca-3', respectively), one-tube multiplex PCR was carried out in a volume of 20 μl containing 0.1 μg of genomic DNA.…”

Functional promoter polymorphisms of macrophage migration inhibitory factor in peptic ulcer diseases

“…Sample stocked DNAs isolated from biopsy specimens or peripheral blood were used. Polymorphism was genotyped by PCR-SSCP method as reported previously (18,19). To detect -794 CATT repeats, using the primer pair (MIFTRF, 5'-TGATCCAGTTGCTGCCTTGTC-3', and MIFTRR, 5'-TCCACTAATGGTAAACTCGGGGAC-3'), PCR was carried out in a volume of 20 μl containing 0.1 μg of genomic DNA.…”

“…We have already reported the close association between MIF promoter polymorphisms and gastric mucosal atrophy followed by gastric carcinogenesis (18,19). However, the roles of these polymorphisms in the development of gastro-duodenal peptic ulceration remain unclear.…”