Misener Virginia L, Gomez Lissette, Wigg Karen G, King Nicole, Kiss Enikõ, Daróczi Gabriella, Kapornai Krisztina, Tamás Zsuzsanna, Mayer László, Gádoros Júlia, Baji Ildikó, Kennedy James L, Kovacs Maria, Vetró Agnes, Barr Cathy L
Toronto Western Research Institute, University Health Network, Ontario, Canada.
Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):653-9. doi: 10.1002/ajmg.b.30885.
Given substantial evidence for IL-1beta involvement in the etiology of depression, the IL1B gene is a strong candidate for involvement in susceptibility to depressive disorders. However, association studies investigating this, to date, have been limited to just two polymorphisms (rs1143627[-31T/C] and rs16944[-511C/T]) that constitute only a fraction of the genetic variation that is actually present across this gene in the population. Here, in a family-based association study of childhood-onset mood disorders (COMD), characterized by onset of depression before the age of 15, we have used a gene-wide approach, employing a panel of five tagging SNPs spanning the entire gene. Based on TDT analyses of both individual alleles and haplotypes, in a study sample of 646 families (with 782 affected children), none of the SNPs, including those implicated in transcriptional regulation of the gene, showed evidence for association with COMD. This is the largest and most comprehensive study of IL1B in relation to mood disorders that has been carried out, to date. The results do not support the involvement of IL1B as a major factor in genetic risk for early-onset mood disorders.
鉴于有大量证据表明白细胞介素-1β（IL-1β）参与抑郁症的病因，白细胞介素1B（IL1B）基因是参与抑郁症易感性的有力候选基因。然而，迄今为止，针对此的关联研究仅限于两个多态性位点（rs1143627[-31T/C]和rs16944[-511C/T]），而这仅占该基因在人群中实际存在的遗传变异的一小部分。在此，在一项基于家庭的儿童期起病情绪障碍（COMD，其特征为15岁前出现抑郁发作）关联研究中，我们采用了全基因方法，使用了一组跨越整个基因的五个标签单核苷酸多态性（SNP）。基于对单个等位基因和单倍型的传递不平衡检验（TDT）分析，在一个由646个家庭（有782名患病儿童）组成的研究样本中，没有一个SNP，包括那些与该基因转录调控有关的SNP，显示出与COMD相关的证据。这是迄今为止进行的关于IL1B与情绪障碍关系的规模最大、最全面的研究。结果不支持IL1B作为早发性情绪障碍遗传风险的主要因素。
