人类Rho鸟嘌呤核苷酸交换因子11基因与日本人群的精神分裂症有关。
Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population.
作者信息
Mizuki Yutaka, Takaki Manabu, Okahisa Yuko, Sakamoto Shinji, Kodama Masafumi, Ujike Hiroshi, Uchitomi Yosuke
机构信息
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
出版信息
Hum Psychopharmacol. 2014 Nov;29(6):552-8. doi: 10.1002/hup.2435. Epub 2014 Oct 15.
OBJECTIVE
The human Rho guanine nucleotide exchange factor 11 (ARHGEF11) gene is one of the candidate genes for type 2 diabetes mellitus (T2DM). ARHGEF11 is mapped to chromosome 1q21, which has susceptible risk loci for T2DM and schizophrenia. We hypothesized that ARHGEF11 contributes to the pathogenesis of schizophrenia.
METHOD
We selected eight single nucleotide polymorphisms of ARHGEF11 that had significant associations with T2DM for a case-control association study of 490 patients with schizophrenia and 500 age-matched and sex-matched controls.
RESULTS
We did not find any differences in allelic, genotypic associations, or minor allele frequencies with schizophrenia. Analysis of the rs6427340-rs6427339 haplotype and the rs822585-rs6427340-rs6427339 haplotype combination provided significant evidence of an association with schizophrenia (global permutations p = 0.00047 and 0.0032, respectively). C-C of the rs6427340-rs6427339 haplotype and A-C-C of the rs822585-rs6427340-rs6427339 haplotype carried higher risk factors for schizophrenia (permutation p = 0.0010 and 0.0018, respectively). A-C-T of the rs822585-rs6427340-rs6427339 haplotype had a possible protective effect (permutation p = 0.031).
CONCLUSION
These results provide new evidence that ARHGEF11 may constitute a risk factor for schizophrenia.
目的
人类Rho鸟嘌呤核苷酸交换因子11（ARHGEF11）基因是2型糖尿病（T2DM）的候选基因之一。ARHGEF11定位于1q21染色体，该染色体存在T2DM和精神分裂症的易感风险位点。我们推测ARHGEF11参与了精神分裂症的发病机制。
方法
我们选择了与T2DM有显著关联的8个ARHGEF11单核苷酸多态性，对490例精神分裂症患者和500例年龄及性别匹配的对照进行病例对照关联研究。
结果
我们未发现等位基因、基因型关联或次要等位基因频率在精神分裂症患者与对照之间存在差异。对rs6427340 - rs6427339单倍型和rs822585 - rs6427340 - rs6427339单倍型组合的分析提供了与精神分裂症相关的显著证据（全局置换p值分别为0.00047和0.0032）。rs6427340 - rs6427339单倍型的C - C以及rs822585 - rs6427340 - rs6427339单倍型的A - C - C携带精神分裂症的较高风险因素（置换p值分别为0.0010和0.0018）。rs822585 - rs6427340 - rs6427339单倍型的A - C - T具有可能的保护作用（置换p值 = 0.031）。
结论
这些结果提供了新的证据，表明ARHGEF11可能是精神分裂症的一个风险因素。
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