Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome

Abstract

Irritable Bowel Syndrome (IBS) is characterized by abdominal pain and alterations in bowel pattern, such as constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Since malabsorption of ingested carbohydrates (CHO) can cause abdominal symptoms that closely mimic those of IBS, identifying genetic mutations in CHO digestive enzymes associated with IBS symptoms is critical to ascertain IBS pathophysiology. Through candidate gene association studies, we identify several common variants in TREH, SI, SLC5A1 and SLC2A5 that are associated with IBS symptoms. By investigating rare recessive Mendelian or oligogenic inheritance patterns, we identify case-exclusive rare deleterious variation in known disease genes (SI, LCT, ALDOB, and SLC5A1) as well as candidate disease genes (MGAM and SLC5A2), providing potential evidence of monogenic or oligogenic inheritance in a subset of IBS cases. Finally, our data highlight that moderate to severe IBS-associated gastrointestinal symptoms are often observed in IBS cases carrying one or more of deleterious rare variants.

Efficacy and safety of a Low-FODMAP combined with gluten-free diet in adult irritable bowel syndrome: a systematic review and meta-analysis

“…Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by chronic abdominal pain, bloating, and altered bowel habits [1] . It signi cantly affects the quality of life for patients and poses a substantial burden on healthcare systems worldwide [2] . Despite its high prevalence, the etiology and pathophysiology of IBS remain unclear, and treatment options often provide limited relief [3] .…”