Center for Eating Disorders Ursula, Leidschendam, The Netherlands.
Genes Brain Behav. 2011 Mar;10(2):236-43. doi: 10.1111/j.1601-183X.2010.00660.x. Epub 2010 Nov 22.
Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.
双生子研究表明，遗传因素在神经性厌食症（AN）和自我诱导呕吐（SV）中起重要作用，而 SV 是不同类型进食障碍（ED）共有的一个关键症状。我们研究了 25 个单核苷酸多态性（SNP）与 AN 和 ED 之间的关联，这些 SNP 可捕获候选基因（Stathmin 1 [STMN1]、5-羟色胺受体 1D [HTR1D]、色氨酸羟化酶 2 [TPH2] 和脑源性神经营养因子 [BDNF]）中 71-91%的常见变异。首先比较了所有 SNP 的第一个等位基因频率在荷兰病例组（182 例 AN、149 例 SV 型 ED）和 607 名对照者之间的差异。对本研究初始结果中 P 值 < 0.05 的关联进行了进一步的元分析，该分析采用了另外两个独立的 ED 病例对照样本，这两个样本共提供了 887 例 AN 病例、306 例 SV 型 ED 病例和 1914 例对照者。色氨酸羟化酶 2 rs1473473 的次要 C 等位基因在 AN [比值比（OR）=1.30，95%置信区间（CI）1.08-1.57，P < 0.003]和 SV 型 ED [OR = 1.52，95% CI 1.28-2.04，P < 0.006]中均具有显著效应。在合并病例组中，rs1473473 存在显性效应（OR = 1.38，95% CI 1.16-1.64，P < 0.0003）。元分析表明，色氨酸羟化酶 2 多态性 rs1473473 与 AN、SV 型 ED 以及合并组的风险增加相关。
