Researchers identify genetic biomarker linked to risk for severe ulcerative colitis
Click Here to Manage Email Alerts
Key takeaways:
- The human leukocyte antigen DRB1*01:03 allele was associated with ulcerative colitis requiring major operation, hospitalization and corticosteroid use.
- This association persisted 3 years after diagnosis.
The human leukocyte antigen DRB1*01:03 allele was associated with severe ulcerative colitis, along with greater odds for major operation, hospitalization and corticosteroid use, according to results of a Danish study.
“There is a clinical need to identify biomarkers of severe disease to capture subgroups requiring intensified monitoring and treatment to avoid repeat hospitalizations and surgical procedures,” Marie Vibeke Vestergaard, MSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease at Aalborg University in Copenhagen, Denmark, and colleagues wrote in JAMA.
In a nationwide, genome-wide association study, Vestergaard and colleagues included 4,491 Danish patients with UC (mean age at diagnosis, 23.3 years; 53% women) from the Center for Molecular Prediction of Inflammatory Bowel Disease neonatal blood spot cohort (n = 4,153) and the North Denmark Biobank study (n = 338). They conducted genome analysis on 9,508,878 single-nucleotide variations and human leukocyte antigen (HLA) alleles after adjusting for sex, year and age at diagnosis.
At baseline, 27% of patients had severe UC, defined as at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days and/or systemic corticosteroid use ( 5,000 mg) within 3 years of diagnosis.
Study results showed a chromosome 6 locus in the HLA region was significantly associated with severe UC (OR = 2.23; 95% CI, 1.96-2.5). More specifically, the HLA-DRB1*01:03 allele “explained this association” overall (OR = 3.32; 95% CI, 2.24-4.89), as well as in the neonatal blood spot (OR = 3.29; 95% CI, 2.22-4.89) and North Denmark Biobank (OR = 3.98; 95% CI, 0.54-29.23) cohorts.
Compared with noncarriers, HLA-DRB1*01:03 carriers had higher odds for major operations (OR = 6.38; 95% CI, 3.89-10.46), at least two hospitalizations (OR = 5.24; 95% CI, 3.49-7.86) and systemic corticosteroid use (OR = 2.3; 95% CI, 1.42-3.71). Time-to-event analyses showed this association “extended beyond 3 years after diagnosis” with HRs of 2.22 (95% CI, 1.79-2.74), 5.13 (95% CI, 3.86-6.81) and 1.69 (95% CI, 1.38-2.07) for times to hospitalization, major operation and corticosteroid use, respectively.
“Among individuals with ulcerative colitis, HLA-DRB1*01:03 was associated with severe ulcerative colitis requiring major operation, hospitalization and systemic corticosteroid use compared with less severe disease,” Vestergaard and colleagues wrote. “Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis.”
They continued: “Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis.”
Collapse
Read more about
Click Here to Manage Email Alerts