Rao Shuquan, Ye Ning, Hu Huiling, Shen Yan, Xu Qi
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Tsinghua University, Beijing, China.
Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):317-24. doi: 10.1002/ajmg.b.32403. Epub 2016 Jan 22.
Schizophrenia is one of the most severe psychiatric disorders, with a high heritability of up to 80%. Several studies have reported telomere dysfunction in schizophrenia, and common variants in the telomerase reverse transcriptase (TERT) gene. TERT is a key component of the telomerase complex that maintains telomere length by addition of telomere repeats to telomere ends, and has repeatedly shown association with mean lymphocyte telomere length (LTL). Thus, we hypothesized that TERT may be a novel susceptibility gene for schizophrenia. Using a Taqman protocol, we genotyped eight tag SNPs from the TERT locus in 1,072 patients with paranoid schizophrenia and 1,284 control subjects from a Chinese Han population. We also measured mean LTL in 98 cases and 109 controls using a quantitative PCR-based technique. Chi-square tests showed that two SNPs, rs2075786 (P = 0.0009, OR = 0.76, 95%CI = 0.65-0.90) and rs4975605 (P = 0.0026, OR = 0.73, 95%CI = 0.60-0.90), were associated with a protective effect, while rs10069690 was associated with risk of paranoid schizophrenia (P = 0.0044, OR = 1.23, 95%CI = 1.07-1.42). Additionally, the rs2736118-rs2075786 haplotype showed significant association with paranoid schizophrenia (P = 0.0013). Moreover, mean LTL correlated with rs2075786 genotypes was significantly shorter in the patient group than the control group. The present results suggest that the TERT gene may be a novel candidate involved in the development of paranoid schizophrenia.
精神分裂症是最严重的精神疾病之一，遗传度高达80%。多项研究报告了精神分裂症中的端粒功能障碍以及端粒酶逆转录酶（TERT）基因的常见变异。TERT是端粒酶复合物的关键组成部分，通过在端粒末端添加端粒重复序列来维持端粒长度，并多次显示与平均淋巴细胞端粒长度（LTL）相关。因此，我们推测TERT可能是精神分裂症的一个新的易感基因。我们使用Taqman方法，对来自中国汉族人群的1072例偏执型精神分裂症患者和1284例对照者的TERT基因座的8个标签单核苷酸多态性（SNP）进行了基因分型。我们还使用基于定量PCR的技术测量了98例患者和109例对照者的平均LTL。卡方检验显示，两个SNP，rs2075786（P = 0.0009，OR = 0.76，95%CI = 0.65 - 0.90）和rs4975605（P = 0.0026，OR = 0.73，95%CI = 0.60 - 0.90）具有保护作用，而rs10069690与偏执型精神分裂症风险相关（P = 0.0044，OR = 1.23，95%CI = 1.07 - 1.42）。此外，rs2736118 - rs2075786单倍型与偏执型精神分裂症显著相关（P = 0.0013）。而且，患者组中与rs2075786基因型相关的平均LTL明显短于对照组。目前的结果表明，TERT基因可能是参与偏执型精神分裂症发病的一个新候选基因。
