So Hon-Cheong, Chen Ronald Y L, Chen Eric Y H, Cheung Eric F C, Li Tao, Sham Pak C
Department of Psychiatry, University of Hong Kong, Hong Kong, China.
Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):77-85. doi: 10.1002/ajmg.b.30577.
The regulator of G-protein signaling 4 (RGS4) has been suggested as a candidate gene for schizophrenia. However, following an initial positive report, subsequent association studies between RGS4 and schizophrenia have yielded inconclusive results. Also, few studies have investigated the association of RGS4 polymorphisms with the phenotypic subgroups of schizophrenia. To further clarify the role of RGS4 in this disease, we performed a case-control study (504 cases and 531 controls of Han Chinese descent) to examine the association of RGS4 with schizophrenia and with clinical and neurocognitive profiles. The four markers (SNPs 1, 4, 7, and 18) implicated in the original association study were genotyped. We detected significant association of four-marker haplotypes with schizophrenia (UNPHASED: global P = 0.037; PHASE: global P = 0.048). The haplotype G-G-G-G, which was implicated in at least three previous studies, was the major risk haplotype (UNPHASED: P = 0.019; PHASE: P = 0.010). Regarding the clinical phenotypes, the Wechsler Adult Intelligence Test (WAIS) information subtest score was associated with SNP4 genotypes (P = 0.001). PANSS total and global psychopathology scores were also associated with SNP4, but may not reliably reflect the general severity of disease as the scores may be affected by confounders like medication response. Our study provides further support for a role of RGS4 in the pathogenesis of schizophrenia. We identified G-G-G-G as the risk haplotype in our Chinese sample. The association with information subtest score suggests an effect of RGS4 on premorbid functioning, which may be related to neurodevelopmental processes. Further independent studies are required to verify our findings.
G蛋白信号调节因子4（RGS4）已被认为是精神分裂症的候选基因。然而，在最初的阳性报告之后，随后关于RGS4与精神分裂症的关联研究结果并不确定。此外，很少有研究调查RGS4基因多态性与精神分裂症表型亚组的关联。为了进一步阐明RGS4在这种疾病中的作用，我们进行了一项病例对照研究（504例病例和531例汉族对照），以检查RGS4与精神分裂症以及临床和神经认知特征的关联。对最初关联研究中涉及的四个标记（单核苷酸多态性1、4、7和18）进行基因分型。我们检测到四个标记单倍型与精神分裂症有显著关联（UNPHASED：全局P = 0.037；PHASE：全局P = 0.048）。至少在之前三项研究中涉及的G-G-G-G单倍型是主要风险单倍型（UNPHASED：P = 0.019；PHASE：P = 0.010）。关于临床表型，韦氏成人智力量表（WAIS）信息子测试得分与单核苷酸多态性4基因型相关（P = 0.001）。阳性和阴性症状量表（PANSS）总分和总体精神病理学得分也与单核苷酸多态性4相关，但可能无法可靠地反映疾病的总体严重程度，因为这些得分可能受到药物反应等混杂因素的影响。我们的研究为RGS4在精神分裂症发病机制中的作用提供了进一步支持。我们在中国样本中确定G-G-G-G为风险单倍型。与信息子测试得分的关联表明RGS4对病前功能有影响，这可能与神经发育过程有关。需要进一步的独立研究来验证我们的发现。
