title: Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study.
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.
authors.affiliation: Children's Hospital Boston, MA 02115, USA. Jessica.lee@childrens.harvard.edu
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Essers
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Escher
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.forename: Johannah L
authors.initials: JL
authors.lastname: Butler
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stephens
authors.forename: Marco F
authors.initials: MF
authors.lastname: Ramoni
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Grand
authors.forename: Joel
authors.initials: J
authors.lastname: Hirschhorn
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006130:Growth Disorders / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010865:Pilot Projects; D011506:Proteins / Q000378:metabolism; D044465:White People
chemical_list: C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins