New Method to Detect Defective Gene in Inflammatory Bowel Disorder Patients

A new method to identify the loss of function of the PTPN2 gene (mutation) that was common in patients with inflammatory bowel disease (IBD) has been developed by University of California researchers. The findings of the study are published in the journal of clinical investigations. About 3 million Americans are affected with IBD (chronic intestinal disease) where the lining of gut becomes inflamed and leaky.

A new method has identified that the mutation of the PTPN2 gene is responsible for the leaky gut. The mutation of the gene increases the activity of claudin-2 (protein that causes loss of water and sodium into the gut and promotes diarrhea). This was identified by using mouse models, the PTPN2 gene acts as a brake for the expression of the claudin-2 protein. The mutation of the PTPN2 gene removes the break and allows increased fluid loss.

In addition, PTPN2 also promotes an endogenous factor, called matriptase, that removes claudin-2 from the area of the cell membrane where it mediates its effects in allowing fluid loss to occur,” says McCole – professor at UCR school of Medicine.

The defect of the PTPN2 gene can be reversed by treating the cells that lack the gene with recombinant or synthetic matriptase.

According to McCole “Our work improves understanding of how the genetics of IBD can contribute to the altered physiology in patients that drives their symptoms,” “It also supports our related work identifying how the class of drugs, called JAK inhibitors, may be used to rescue ‘leaky gut,’ particularly in patients with loss-of-function mutations in the PTPN2 gene.”

Research has also shown that the mutation in the PTPN2 gene causes gut epithelial damage in children and increases gut epithelial leakiness.

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Source: Medindia