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首页> 外文期刊>Annals of Human Genetics >Association of Linear Growth Impairment in Pediatric Crohn's Disease and a Known Height Locus: A Pilot Study
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Association of Linear Growth Impairment in Pediatric Crohn's Disease and a Known Height Locus: A Pilot Study

机译：小儿克罗恩病线性增长障碍与已知身高轨迹的关联：一项初步研究

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SummaryThe 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.
机译：总结营养，激素和/或疾病相关因素未能充分解释克罗恩病（CD）的生长障碍的病因，这表明遗传因素可能是另一个原因。这项横断面研究的目的是研究与儿童发作性CD线性生长相关的遗传变异。我们对951名受试者（317名CD患者-父母三人组）中14种CD易感性和23个与身材相关的基因座内的64种多态性进行了基因分型。患者年龄高度Z分数<-1.64被用于将先证者分为生长障碍和非生长障碍组。传输不平衡测试（TDT）用于研究与生长障碍的关联。 CD的生长障碍（年龄高的Z分数<-1.64）与dymeclin基因DYM（rs8099594）的身材相关的多态性之间存在显着关联（OR = 3.2，CI [1.57–6.51]，p = 0.0007）。此外，在生长受损的CD患儿中，有两个CD易感性等位基因10q21.1基因间区域（rs10761659）和ATG16L1（rs10210302）的名义过量传播（OR = 2.36，CI [1.26-4.41] p = 0.0056和OR = 2.45，CI [1.22-4.95] p = 0.0094）。我们的数据表明，与身材相关的和可能的CD风险等位基因引起的遗传影响可能使CD患者容易发生线性生长改变。这是有关身高相关基因座与CD生长障碍之间联系的第一份报告。

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  • 来源
    《Annals of Human Genetics》 |2010年第6期|p.489-497|共9页
  • 作者

    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;

  • 作者单位

    Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, MA 02115, USA;

    Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, MA 02115, USA|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;

    Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, GA 03022, USA;

    Department of Pediatric Gastroenterology, Erasmus MC- Sophia Children's Hospital, Rotterdam, the Netherlands;

    Montreal Heart Institute, Quebec, Canada;

    Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital Boston, Boston, MA 02115, USA;

    Division of Gastroenterology and Nutrition, Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA;

    Children's Hospital Informatics Program, Children's Hospital Boston, Boston, MA 02115, USA|Harvard-MIT Division of Health Sciences and;

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  • 关键词

    Height; growth retardation; inflammatory bowel disease; DYM; dymeclin;

    机译：身高;生长发育迟缓;炎症性肠病;DYM;dymeclin;

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