The Second Affiliated Hospital of Xinxiang Medical University, China.
Int J Psychiatry Med. 2013;45(3):269-78. doi: 10.2190/PM.45.3.f.
Recent genome wide association studies (GWASs) assessing the relationship between schizophrenia (SZ) and the ZNF804A gene, particularly the single nucleotide polymorphism (SNP) rs1344706, have yielded conflicting results. Schizophrenia is a heterogeneous disorder, so it is possible that an association may be restricted to specific SZ subtypes and that population heterogeneity may obscure a contribution of ZNF804A allelic variation to SZ risk. We thus evaluated the association between rs1344706 and different clinical SZ subtypes in a large Han Chinese patient population.
The rs1344706 genotype was determined in 1,025 SZ patients and 977 healthy controls using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLPs). The clinical SZ subtypes included paranoid, catatonic, disintegrated, and undifferentiated, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition IV (DSM-IV).
No significant differences in genotype and allele frequencies were found between controls and either the total SZ population (A > C, chi2 = 4.339, 2.994; p = 0.227, 0.087, respectively) or paranoid SZ patients (chi2 = 2.053, 0.002; p = 0.562, 0.973, respectively). However, there was a significant association between genotype frequency and SZ subtype (chi2 = 12.632, p = 0.049).
We found no evidence that the ZNF804A SNP rs1344706 is a susceptibility locus for SZ. However, conflicting results from previous association studies may be due to genetic heterogeneity between different patient SZ subtypes.
最近的全基因组关联研究(GWAS)评估了精神分裂症(SZ)与 ZNF804A 基因之间的关系,特别是单核苷酸多态性(SNP)rs1344706,其研究结果存在冲突。精神分裂症是一种异质性疾病,因此关联可能仅限于特定的 SZ 亚型,而人群异质性可能掩盖了 ZNF804A 等位基因变异对 SZ 风险的贡献。因此,我们在一个大型汉族患者群体中评估了 rs1344706 与不同临床 SZ 亚型之间的关联。
使用聚合酶链反应限制片段长度多态性(PCR-RFLP)法,在 1025 例 SZ 患者和 977 例健康对照中确定 rs1344706 基因型。根据《精神障碍诊断与统计手册-第四版》(DSM-IV)诊断的偏执型、紧张型、瓦解型和未分化型,将 SZ 临床亚型包括在内。
在对照组与总 SZ 人群(A > C,chi2 = 4.339,2.994;p = 0.227,0.087,分别)或偏执型 SZ 患者(chi2 = 2.053,0.002;p = 0.562,0.973,分别)之间,基因型和等位基因频率均无显著差异。然而,基因型频率与 SZ 亚型之间存在显著关联(chi2 = 12.632,p = 0.049)。
我们没有发现 ZNF804A SNP rs1344706 是 SZ 易感基因座的证据。然而,先前关联研究的结果存在冲突,可能是由于不同患者 SZ 亚型之间的遗传异质性所致。