HLA-DQ genotype is associated with accelerated small bowel transit in patients with diarrhea-predominant irritable bowel syndrome

Abstract

Colonic transit (CT) is accelerated in 46% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Improvement in IBS-D with gluten withdrawal is associated with human leukocyte antigen (HLA)-DQ2 positivity; the mechanism of improvement is unclear. To determine if HLA-DQ2-positive or HLA-DQ8-positive patients with IBS-D have faster small bowel (SB) or CT than HLA-DQ2-negative and HLA-DQ8-negative patients. Among 94 patients with IBS-D, who previously provided DNA samples, 64 had undergone validated measurements of CT [geometric center at 24 h (GC24)]; 50 of the patients also had measurement of gastric emptying (GE) and 54 of SB transit (colonic filling at 6 h). HLA-DQ status was determined by tag single nucleotide polymorphism approach. Associations of colonic filling at 6 h and GC24 with HLA-DQ2 and HLA-DQ8 status were assessed using analysis of covariance, adjusting for BMI. Mean age was 40.8±1.6 years; 98.5% were females. In 60 of the 64 patients, celiac disease was excluded by serology or histology. There were no significant differences in age or BMI among the different HLA-DQ groups. Independently, patients positive for HLA-DQ2 had numerically greater colonic filling at 6 h compared with HLA-DQ2-negative (P=0.065), and those positive for HLA-DQ8 had greater colonic filling at 6 h compared with HLA-DQ8-negative patients (P=0.021). Gastric emptying was not associated with HLA-DQ2 and HLA-DQ8 status. Patients positive for both HLA-DQ2 and HLA-DQ8 had greater colonic filling at 6 h (P=0.013) and numerically higher, but not significant, GC24 (P=0.38) compared with HLA-DQ2-negative and HLA-DQ8-negative patients. Patients with IBS-D positive for HLA-DQ8 or for both HLA-DQ2 and HLA-DQ8 have faster SB transit. The mechanism of the accelerated SB transit and the effect of gluten withdrawal on SB function in IBS-D deserve further investigation.