Baritaki S, Rizos E, Zafiropoulos A, Soufla G, Katsafouros K, Gourvas V, Spandidos D A
Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
Eur J Hum Genet. 2004 Jul;12(7):535-41. doi: 10.1038/sj.ejhg.5201180.
Schizophrenia is a severe and common psychiatric disorder afflicting 1% of the world population. A role of many neurotransmitter receptors in schizophrenia was suggested by an association with several polymorphisms located in their coding regions. In this study we examined the contribution of the T-102C and A-206G transitions in the 5-HTR2a and DRD3 receptor genes respectively to genetic susceptibility and phenotypic expression of schizophrenia disorder within the Greek population. We determined by PCR and RFLP analysis the genotype for the above polymorphisms in 114 schizophrenic hospitalized individuals and 192 control samples. In contrast to previous reports from large European multicentre studies, which indicate significant correlation between schizophrenia and C-102 allele of the T-102C polymorphism, in this study we observed a statistically significant overall association between the disorder and allele T-102 (P<0.0001, odds ratio (OR)=2.11, 95% CI=1.48-3.02). We also found a highly significant excess of the T-102/C-102 and C-102/C-102 genotypes in the normal group (P<0.001). Comparison of the patients with the controls for the DRD3 polymorphism (A-206G transition) showed marginally nonsignificant differences in the genotypic (P=0.054) and no significance in the allelic (P=0.163) frequencies. However, the A-206/A-206 genotype seems to positively contribute to the disorder appearance, when compared to A-206/G-206 as genotype base line risk (P=0.016, OR=1.88, 95% CI=1.09-3.26). In conclusion, from genetic association analysis of this schizophrenic population, a significant association is clearly determined between the HTR2 genetic polymorphism and the presence of schizophrenic disorder, manifested as increased risk of schizophrenia for carriers of the T-102 allele.
精神分裂症是一种严重且常见的精神疾病，影响着全球1%的人口。许多神经递质受体在精神分裂症中的作用是通过与位于其编码区域的几种多态性的关联而被提出的。在本研究中，我们分别研究了5 - HTR2a和DRD3受体基因中的T - 102C和A - 206G转换对希腊人群中精神分裂症的遗传易感性和表型表达的贡献。我们通过PCR和RFLP分析确定了114名住院精神分裂症患者和192个对照样本中上述多态性的基因型。与来自大型欧洲多中心研究的先前报告相反，那些报告表明精神分裂症与T - 102C多态性的C - 102等位基因之间存在显著相关性，而在本研究中，我们观察到该疾病与T - 102等位基因之间存在统计学上显著的总体关联（P < 0.0001，优势比（OR）= 2.11，95%置信区间= 1.48 - 3.02）。我们还发现正常组中T - 102/C - 102和C - 102/C - 102基因型显著过量（P < 0.001）。对患者与对照进行DRD3多态性（A - 206G转换）比较，结果显示基因型频率差异边缘不显著（P = 0.054），等位基因频率差异无显著性（P = 0.163）。然而，与作为基因型基线风险的A - 206/G - 206相比，A - 206/A - 206基因型似乎对疾病的出现有正向贡献（P = 0.016，OR = 1.88，95%置信区间= 1.09 - 3.26）。总之，通过对该精神分裂症人群的遗传关联分析，明确确定了HTR2基因多态性与精神分裂症的存在之间存在显著关联，表现为T - 102等位基因携带者患精神分裂症的风险增加。
