Bachner-Melman Rachel, Lerer Elad, Zohar Ada H, Kremer Ilana, Elizur Yoel, Nemanov Lubov, Golan Moria, Blank Shulamit, Gritsenko Inga, Ebstein Richard P
Department of Psychology, Mount Scopus, Hebrew University, Jerusalem, Israel.
Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):748-56. doi: 10.1002/ajmg.b.30505.
The dopamine D4 receptor (DRD4), a well-characterized, polymorphic gene, is an attractive candidate for contributing risk to disordered eating and anorexia nervosa (AN). We tested association using UNPHASED for 5 DRD4 polymorphic loci, 3 promoter region SNPs (C-521T, C-616G, A-809G), the 120 bp promoter region tandem duplication and the exon III repeat, in 202 AN trios and 418 control families. Since perfectionism characterizes AN, we tested these five loci for association with the Child and Adolescent Perfectionism Scale (CAPS) in the AN and control groups. Single locus analysis showed significant association between the 'C' C-521T allele and AN. Haplotype analysis also showed significant association, particularly a 4-locus haplotype (exon III&120 bp repeat&C-521T&A-809G). Association was also observed between DRD4 and CAPS scores both for AN and control subjects. The insulin-like growth factor 2 (IGF2) and the arginine vasopressin 1a receptor (AVPR1a), previously shown to be associated with disordered eating, were also associated with CAPS scores. Three genes associated with AN were also associated with perfectionism. Personality traits are potential endophenotypes for understanding the etiology of eating disorders and one of the several pathways to eating pathology may be mediated by the impact of DNA sequences on perfectionism.
多巴胺D4受体（DRD4）是一个特征明确的多态性基因，是导致饮食失调和神经性厌食症（AN）风险增加的一个有吸引力的候选基因。我们使用UNPHASED软件，对202个AN三联体和418个对照家庭中的5个DRD4多态性位点进行了关联测试，这5个位点包括3个启动子区域单核苷酸多态性（C-521T、C-616G、A-809G）、120bp启动子区域串联重复序列以及外显子III重复序列。由于完美主义是AN的特征之一，我们在AN组和对照组中测试了这五个位点与儿童及青少年完美主义量表（CAPS）的关联性。单基因座分析显示，“C”型C-521T等位基因与AN之间存在显著关联。单倍型分析也显示出显著关联，特别是一个包含4个基因座的单倍型（外显子III&120bp重复序列&C-521T&A-809G）。在AN组和对照组中，DRD4与CAPS评分之间也观察到了关联。胰岛素样生长因子2（IGF2）和精氨酸加压素1a受体（AVPR1a），先前已证明与饮食失调有关，也与CAPS评分相关。三个与AN相关的基因也与完美主义相关。人格特质是理解饮食失调病因的潜在内表型，饮食病理学的几种途径之一可能是由DNA序列对完美主义的影响所介导的。
