Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
Mol Biol Rep. 2012 Jun;39(6):6875-80. doi: 10.1007/s11033-012-1513-3. Epub 2012 Feb 7.
Thrombospondin 1 (THBS1), a multi-domain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. Increasing evidence has suggested that not only various markers for synaptic pathology, but also astrocytes are affected in schizophrenia. In this study, we investigated whether coding region single nucleotide polymorphisms (cSNPs) of the THBS1 gene were associated with schizophrenia and with the clinical symptoms of schizophrenia patients. We genotyped two cSNPs [rs2228261 (Asn470Asn) and rs2292305 (Thr523Ala)] using direct sequencing in 220 schizophrenia patients and 376 control subjects. In this study, rs2228261 revealed significant association with schizophrenia in both codominant (TT vs. CC, P = 0.009, OR = 2.10, 95% CI = 1.23-3.59) and recessive models (TT vs. CC/CT, P = 0.0012, OR = 2.28, 95% CI = 1.38-3.77). Also, rs2292305 was associated with schizophrenia in the recessive model (GG vs. AA/AG, P = 0.0052, OR = 2.05, 95% CI = 1.24-3.38). Additionally, in the analysis of the haplotype, the CA and TG haplotypes consisting of rs2228261 and rs2292305 were associated with schizophrenia in the dominant (P = 0.019, OR = 1.79, 95% CI = 1.10-2.90) and recessive models, respectively (P = 0.0086, OR = 0.51, 95% CI = 0.31-0.84). In further analysis according to the clinical symptoms, rs2292305 showed a weak association with the poor concentration symptoms of schizophrenia patients in the dominant model (AG/GG vs. AA, P = 0.024, OR = 2.04, 95% CI = 1.09-3.83). The results suggest that the THBS1 gene may contribute to the susceptibility of schizophrenia.
血小板反应蛋白 1（THBS1）是一种多结构域糖蛋白，由星形胶质细胞分泌，可促进突触发生。越来越多的证据表明，不仅各种突触病理学标志物，而且星形胶质细胞也受精神分裂症影响。在这项研究中，我们研究了 THBS1 基因的编码区单核苷酸多态性（cSNP）是否与精神分裂症以及精神分裂症患者的临床症状有关。我们使用直接测序在 220 名精神分裂症患者和 376 名对照中对两个 cSNP [rs2228261（Asn470Asn）和 rs2292305（Thr523Ala）]进行了基因分型。在这项研究中，rs2228261 在显性（TT 与 CC，P = 0.009，OR = 2.10，95%CI = 1.23-3.59）和隐性模型（TT 与 CC/CT，P = 0.0012，OR = 2.28，95%CI = 1.38-3.77）中与精神分裂症显著相关。此外，rs2292305 在隐性模型（GG 与 AA/AG，P = 0.0052，OR = 2.05，95%CI = 1.24-3.38）中与精神分裂症相关。此外，在单倍型分析中，由 rs2228261 和 rs2292305 组成的 CA 和 TG 单倍型在显性（P = 0.019，OR = 1.79，95%CI = 1.10-2.90）和隐性模型中与精神分裂症相关（P = 0.0086，OR = 0.51，95%CI = 0.31-0.84）。在根据临床症状进行的进一步分析中，rs2292305 在显性模型中与精神分裂症患者注意力不集中症状较弱相关（AG/GG 与 AA，P = 0.024，OR = 2.04，95%CI = 1.09-3.83）。结果表明，THBS1 基因可能与精神分裂症的易感性有关。
