Department of Neuropsychiatry, Seoul National University Hospital, Korea.
Exp Mol Med. 2012 Feb 29;44(2):121-9. doi: 10.3858/emm.2012.44.2.007.
The early growth response gene 2 (EGR2) is located at chromosome 10q21, one of the susceptibility loci in bipolar disorder (BD). EGR2 is involved in cognitive function, myelination, and signal transduction related to neuregulin-ErbB receptor, Bcl-2 family proteins, and brain-derived neurotrophic factor. This study investigated the genetic association of the EGR2 gene with BD and schizophrenia (SPR) in Korea. In 946 subjects (350 healthy controls, 352 patients with BD, and 244 with SPR), nine single nucleotide polymorphisms (SNPs) in the EGR2 gene region were genotyped. Five SNPs showed nominally significant allelic associations with BD (rs2295814, rs61865882, rs10995315, rs2297488, and rs2297489), and the positive associations of all except rs2297488 remained significant after multiple testing correction. Linkage disequilibrium structure analysis revealed two haplotype blocks. Among the common identified haplotypes (frequency > 5%), 'T-G-A-C-T (block 1)' and 'A-A-G-C (block 2)' haplotypes were over-represented, while 'C-G-G-T-T (block 1)' haplotype was under-represented in BD. In contrast, no significant associations were found with SPR. Although an extended analysis with a larger sample size or independent replication is required, these findings suggest a genetic association of EGR2 with BD. Combined with a plausible biological function of EGR2, the EGR2 gene is a possible susceptibility gene in BD.
早期生长反应基因 2（EGR2）位于 10 号染色体 q21，是双相情感障碍（BD）的易感基因之一。EGR2 参与认知功能、髓鞘形成以及与神经调节素-ErbB 受体、Bcl-2 家族蛋白和脑源性神经营养因子相关的信号转导。本研究在韩国人群中调查了 EGR2 基因与 BD 和精神分裂症（SPR）的遗传关联。在 946 名受试者（350 名健康对照者、352 名 BD 患者和 244 名 SPR 患者）中，对 EGR2 基因区域的 9 个单核苷酸多态性（SNP）进行了基因分型。5 个 SNP 与 BD 表现出名义上显著的等位基因关联（rs2295814、rs61865882、rs10995315、rs2297488 和 rs2297489），除 rs2297488 外，所有阳性关联在多重检验校正后仍具有统计学意义。连锁不平衡结构分析显示存在两个单倍型块。在常见的鉴定单倍型（频率>5%）中，'T-G-A-C-T（块 1）'和'A-A-G-C（块 2）'单倍型过度表达，而'C-G-G-T-T（块 1）'单倍型在 BD 中表达不足。相反，与 SPR 无显著关联。尽管需要更大样本量的扩展分析或独立复制来验证，但这些发现提示 EGR2 与 BD 存在遗传关联。结合 EGR2 合理的生物学功能，该基因可能是 BD 的易感基因之一。
