Which gene, encoding an intracellular receptor for muramyl dipeptide that senses bacterial peptidoglycan, is the best-established susceptibility locus for Crohn disease, particularly ileal involvement?

• A HLA-DQA1
• B ATG16L1
• C IL23R
• D NOD2/CARD15 ✓

Explanation

NOD2/CARD15 was the first major susceptibility gene identified for Crohn disease. It encodes a cytosolic pattern recognition receptor that recognizes muramyl dipeptide from bacterial peptidoglycan, and mutations impair innate bacterial handling in Paneth cells, linking it especially to ileal and fibrostenotic disease. ATG16L1 and IL23R are also validated Crohn loci but carry weaker associations and different functions in autophagy and Th17 signaling respectively. HLA variants associate more strongly with ulcerative colitis than with Crohn disease.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.