Association of Linear Growth Impairment in Pediatric Crohn's Disease and a Known Height Locus: A Pilot Study |
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| Authors: | Jessica J Lee Jonah B Essers Subra Kugathasan Johanna C Escher Guillaume Lettre Johannah L Butler Michael C Stephens Marco F Ramoni Richard J Grand Joel Hirschhorn |
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| Institution: | 1. Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, MA 02115, USA;2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;3. Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, GA 03022, USA;4. Department of Pediatric Gastroenterology, Erasmus MC‐ Sophia Children's Hospital, Rotterdam, the Netherlands;5. Montreal Heart Institute, Quebec, Canada;6. Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital Boston, Boston, MA 02115, USA;7. Division of Gastroenterology and Nutrition, Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA;8. Children's Hospital Informatics Program, Children's Hospital Boston, Boston, MA 02115, USA;9. Harvard‐MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA;10. Clinical and Translational Study Unit, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA |
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| Abstract: | The etiology of growth impairment in Crohn's disease (CD) has been inadequately explained by nutritional, hormonal, and/or disease‐related factors, suggesting that genetics may be an additional contributor. The aim of this cross‐sectional study was to investigate genetic variants associated with linear growth in pediatric‐onset CD. We genotyped 951 subjects (317 CD patient–parent trios) for 64 polymorphisms within 14 CD‐susceptibility and 23 stature‐associated loci. Patient height‐for‐age Z‐score < ?1.64 was used to dichotomize probands into growth‐impaired and nongrowth‐impaired groups. The transmission disequilibrium test (TDT) was used to study association to growth impairment. There was a significant association between growth impairment in CD (height‐for‐age Z‐score < ?1.64) and a stature‐related polymorphism in the dymeclin gene DYM (rs8099594) (OR = 3.2, CI 1.57–6.51], p = 0.0007). In addition, there was nominal over‐transmission of two CD‐susceptibility alleles, 10q21.1 intergenic region (rs10761659) and ATG16L1 (rs10210302), in growth‐impaired CD children (OR = 2.36, CI 1.26–4.41] p = 0.0056 and OR = 2.45, CI 1.22–4.95] p = 0.0094, respectively). Our data indicate that genetic influences due to stature‐associated and possibly CD risk alleles may predispose CD patients to alterations in linear growth. This is the first report of a link between a stature‐associated locus and growth impairment in CD. |
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| Keywords: | Height growth retardation inflammatory bowel disease DYM dymeclin |
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