A Klothoβ variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea.

ABSTRACT:

Background & aims

Bile acid (BA) malabsorption of moderate severity is reported in 32% of patients with chronic unexplained diarrhea, including diarrhea-predominant irritable bowel syndrome (IBS-D). We hypothesized that variants of genes regulating hepatic BA synthesis play a role in IBS-D.

Methods

In 435 IBS and 279 healthy subjects, we tested individual associations of 15 common single nucleotide polymorphisms (SNPs) from 7 genes critical to BA homeostasis with symptom-based subgroups using dominant genetic models. In a subset of 238 participants, we tested association with colonic transit. SNP-SNP interactions were investigated based on known protein interactions in BA homeostasis. The function of SNP rs17618244 in Klothoβ (KLB) was evaluated using a protein stability ass

SUBMITTER: Wong BS 

PROVIDER: S-EPMC3109206 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature