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Sci Rep. 2018 Jul 5;8(1):10158. doi: 10.1038/s41598-018-28586-5.

Increased risk for inflammatory bowel disease in congenital hypothyroidism supports the existence of a shared susceptibility factor.

Author information

1
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109, USA.
2
Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan, 48109, USA.
3
Department of Pediatrics and Communicable Diseases, Division of Pediatric Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, 48109, USA.
4
Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, Michigan, 48109, USA.
5
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109, USA. jykao@umich.edu.
6
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109, USA. awaljee@med.umich.edu.
7
Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan, 48109, USA. awaljee@med.umich.edu.

Abstract

Loss-of-function mutations in dual oxidase (DUOX) 2 are the most common genetic variants found in congenital hypothyroidism (CH), and similar mutations have been recently reported in few very-early-onset inflammatory bowel disease (IBD) patients without CH. If DUOX2 variants indeed increase susceptibility for IBD, the enrichment of DUOX2 mutation carriers among CH patients should be reflected in higher risk for developing IBD. Using a database containing health insurance claims data for over 230 million patients in the United States, 42,922 subjects with CH were identified based on strict inclusion criteria using diagnostic codes. For subgroup analysis, CH patients with pharmacy records were stratified as transient or permanent CH based on the absence or presence of levothyroxine treatment, respectively. Patients were matched to an equal-sized, age- and gender-matched non-CH group. Compared to controls, CH patients had a 73% higher overall IBD prevalence (0.52% vs 0.30%; P < 0.0001). The CH-associated relative risk was higher for indeterminate or ulcerative colitis than Crohn's disease. Patients with transient CH had higher odds for IBD (OR 2.39 (95% CI 1.77-3.23) than those with permanent CH (1.69 (95% CI 1.31-2.18). We conclude that patients with CH are at an increased risk of developing IBD. The risk was highest for patients with transient CH, for which partial defects in the DUOX2 system are a particularly common finding.

PMID:
29977049
PMCID:
PMC6033893
DOI:
10.1038/s41598-018-28586-5
[Indexed for MEDLINE]
Free PMC Article

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