Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population

作者：Yutaka Mizuki, Manabu Takaki, Yuko Okahisa, Shinji Sakamoto, Masafumi Kodama, Hiroshi Ujike, Yosuke Uchitomi · 发表于：Human Psychopharmacology Clinical and Experimental · 年份：2014 · DOI：10.1002/hup.2435 · 被引用次数：16 · 研究领域：Genetic Associations and Epidemiology、Schizophrenia research and treatment、Neurotransmitter Receptor Influence on Behavior

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.