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Gene polymorphisms of the macrophage migration inhibitory factor and acute pancreatitis
Rohit Makhija1, Andrew Kingsnorth, Andrew Demaine
1Eastern Deanery, United Kingdom. r_makhija99@hotmail.com
Context:
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is released by macrophages and lymphocytes and plays an important pathogenetic role in acute pancreatitis. It is present in large amounts in the serum and ascitic fluid in rats with experimental pancreatitis and its levels are elevated in humans with pancreatitis. Polymorphisms associated with inflammatory joint diseases exist in the promoter region of the macrophage migration inhibitory factor gene that alter its expression.
Objective:
We investigated the association of macrophage migration inhibitory factor polymorphisms with acute pancreatitis in a population in the UK.
Participants:
A cohort of 164 patients with acute pancreatitis and 197 healthy controls.
Main Outcome Measures:
The -173 G to C single nucleotide polymorphism and the -794 (CATT) n repeat microsatellite were investigated. Restriction fragment length polymorphism (RFLP) was used to assay the -173 polymorphism and PCR followed by polyacrylamide gel electrophoresis (PAGE) was used for the microsatellite.
Results:
The microsatellite did not show any significant differences in distribution between patients and controls. The -173 GG genotype showed a trend towards reduced frequency seen in patients (P=0.056) and the C allele was significantly over expressed in patients (P=0.025). No differences were observed in subgroups based on severity or aetiology of pancreatitis.
Conclusions:
The -173 C allele is over expressed in acute pancreatitis, however studies are needed to explore this further. Our distribution of the microsatellite alleles was quite different to a previously reported Caucasian population and needs further study from viewpoint of population genetics.
Insights
The -173 C allele of macrophage migration inhibitory factor (MIF) is overexpressed in acute pancreatitis patients. Further research is needed to confirm this association and explore population genetics of MIF polymorphisms.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in acute pancreatitis pathogenesis.
- MIF levels are elevated in human pancreatitis and animal models.
- Genetic polymorphisms in the MIF gene promoter can influence its expression.
Purpose of the Study:
- To investigate the association between MIF gene polymorphisms and acute pancreatitis in a UK population.
- To analyze the distribution of specific MIF polymorphisms (-173 G>C and -794 (CATT)n) in patients with acute pancreatitis and healthy controls.
Main Methods:
- Genotyping of 164 acute pancreatitis patients and 197 healthy controls.
- Analysis of the -173 G to C single nucleotide polymorphism using RFLP.
- Analysis of the -794 (CATT)n microsatellite using PCR and PAGE.
Main Results:
- The -794 (CATT)n microsatellite showed no significant difference between patients and controls.
- A trend towards reduced frequency of the -173 GG genotype was observed in patients (P=0.056).
- The -173 C allele was significantly overexpressed in acute pancreatitis patients (P=0.025).
Conclusions:
- The -173 C allele of MIF is associated with an increased risk of acute pancreatitis.
- Further studies are required to validate these findings and explore the population genetics of MIF microsatellite alleles.
- No significant differences were found in subgroups based on pancreatitis severity or etiology.
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