Chen Xiangning, Wang Xu, Sun Cuie, Chen Qi, O'Neill F Anthony, Walsh Dermot, Fanous Ayman, Kendler Kenneth S
Department of Psychiatry, Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia,
Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1231-7. doi: 10.1002/ajmg.b.30759.
FBXL21 gene encodes an F-box containing protein functioning in the SCF ubiquitin ligase complex. The role of the F-box protein is to recruit proteins designated for degradation to the ligase complex so they would be ubiquitinated. Using both family and case-control samples, we found consistent associations in and around FBXL21 gene. In the family sample (Irish study of high density schizophrenia families, ISHDSF, 1,350 subjects from 273 families), a minimal PDT P-value of 0.0011 was observed at rs31555. In the case-control sample (Irish case-control study of schizophrenia, ICCSS, 814 cases and 625 controls), significant associations were observed at two markers (rs1859427 P = 0.0197, and rs6861170 P = 0.0197). In haplotype analyses, haplotype 1-1 (C-T) of rs1859427-rs6861170 was overtransmitted in the ISHDSF (P = 0.0437) and was overrepresented in the ICCSS (P = 0.0177). For both samples, the associated alleles and haplotypes were identical. These data suggested that FBXL21 may be associated with schizophrenia in the Irish samples.
FBXL21基因编码一种在SCF泛素连接酶复合物中发挥作用的含F-Box结构域蛋白。F-Box蛋白的作用是将指定降解的蛋白质招募到连接酶复合物中，使其被泛素化。通过使用家系样本和病例对照样本，我们在FBXL21基因及其周围发现了一致的关联。在家系样本（爱尔兰高密度精神分裂症家系研究，ISHDSF，来自273个家系的1350名受试者）中，在rs31555位点观察到最小的 PDT P值为0.0011。在病例对照样本（爱尔兰精神分裂症病例对照研究，ICCSS，814例病例和625名对照）中，在两个标记位点（rs1859427，P = 0.0197；rs6861170，P = 0.0197）观察到显著关联。在单倍型分析中，rs1859427 - rs6861170的单倍型1-1（C-T）在ISHDSF中过度传递（P = 0.0437），在ICCSS中过度出现（P = 0.0177）。对于两个样本，相关的等位基因和单倍型是相同的。这些数据表明FBXL21可能与爱尔兰样本中的精神分裂症有关。
