Association of Antidiabetic Drug Target Genes with Inflammatory Bowel Disease: A Mendelian Randomization Study.

BACKGROUND

An unmet medical need for the treatment of inflammatory bowel disease (IBD) exists. A part of antidiabetic drugs had potential effects on IBD in various observational research.

OBJECTIVE

To investigate the potential of antidiabetic drugs on IBD.

METHODS

We undertook a summary-data-based Mendelian randomization (SMR) using the expression quantitative trait loci (eQTL) expressed in the blood or colon and a two sample Mendelian randomization (TSMR) utilizing single nucleotide polymorphism (SNP) of antidiabetic drug target genes mediated by blood glucose traits. Participants encompassed patients with IBD (25,042 cases/34,915 controls), UC (12,366 cases/33,609 controls), and CD (12,194 cases/28,072 controls). Data on eQTL in the blood or the colon were from the eQTLGen consortium (31,684 individuals) or GTEx Consortium V8, respectively. SMR was performed by SMR software (20,220,322); the primary method for TSMR was inverse-variance weighted (IVW) or Wald ratio through R studio (2023.06.0+421). Sensitivity analyses were carried out.

RESULTS

A 1-SD upper expression of the gene (target gene of sulfonylureas) in the blood reduced the risk of CD (OR per 1-SD = 0.728, 95% CI = 0.586-0.903, P = 0.004) according to the result of SMR. (target gene of sulfonylureas) expressed in the colon did not affect CD, UC, or IBD. T2D-mediated has a protective effect on CD (OR = 0.475, 95% CI = 0.297-0.761, P = 0.002). Gene predicted no relationship between T2D and CD.

CONCLUSION

Sulfonylureas (SUs) may have side effects on CD. This work provides some suggestions for the selection of antidiabetic drugs in patients with CD.