Lee Jessica J, Essers Jonah B, Kugathasan Subra, Escher Johanna C, Lettre Guillaume, Butler Johannah L, Stephens Michael C, Ramoni Marco F, Grand Richard J, Hirschhorn Joel
Children's Hospital Boston, MA 02115, USA.
Ann Hum Genet. 2010 Nov;74(6):489-97. doi: 10.1111/j.1469-1809.2010.00606.x. Epub 2010 Sep 15.
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.
营养、激素和/或疾病相关因素对克罗恩病（CD）生长发育受损的病因解释并不充分，这表明遗传因素可能是一个额外的影响因素。这项横断面研究的目的是调查与儿童期发病的CD线性生长相关的基因变异。我们对951名受试者（317个CD患者-父母三联体）的14个CD易感基因座和23个身高相关基因座内的64个多态性进行了基因分型。采用患者年龄别身高Z评分＜-1.64将先证者分为生长发育受损组和未受损组。采用传递不平衡检验（TDT）研究与生长发育受损的相关性。CD患者生长发育受损（年龄别身高Z评分＜-1.64）与双微体蛋白基因DYM（rs8099594）中一个与身高相关的多态性之间存在显著相关性（OR=3.2，CI[1.57-6.51]，p=0.0007）。此外，在生长发育受损的CD儿童中，两个CD易感等位基因，即10q21.1基因间区域（rs10761659）和自噬相关基因16样蛋白1（ATG16L1，rs10210302）存在名义上的过度传递（OR分别为2.36，CI[1.26-4.41]，p=0.0056；OR为2.45，CI[1.22-4.95]，p=0.0094）。我们的数据表明，与身高相关以及可能与CD风险等位基因相关的遗传影响可能使CD患者易发生线性生长改变。这是关于身高相关基因座与CD生长发育受损之间联系的首次报道。
