Kremer I, Pinto M, Murad I, Muhaheed M, Bannoura I, Muller D J, Schulze T G, Reshef A, Blanaru M, Gathas S, Goichman R, Rietschel M, Dobrusin M, Bachner-Melman R, Nemanov L, Belmaker R H, Maier W, Ebstein R P
Emek Hospital, Afula, Israel.
Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):35-9. doi: 10.1002/ajmg.b.20008.
COMT is a ubiquitous enzyme crucial to catechol metabolism. The molecular basis of COMT thermolability, that leads to three to fourfold differences in enzyme activity, is due to a substitution of valine with methionine in the Val158/108Met polymorphism. Of special interest is the role of this gene in major psychoses especially since a microdeletion (22q11) containing the COMT gene (velo-cardio-facial syndrome) also carries with it several types of behavioral disorders, including an increased prevalence of schizophrenia. Almost 20 genetic studies have examined the role of COMT in schizophrenia with ambiguous results. Towards clarifying the role of this polymorphism in conferring risk for psychosis, we examined a large group of culturally and ethnically akin Palestinian Arab schizophrenic triads (N = 276) using both a case-control and family-based study. In 194 informative triads with at least one heterozygote parent, no preferential transmission of either COMT allele was observed in this sample (TDT statistic chi-square = 0.14 NS; 131 COMT valine alleles were transmitted and 125 alleles not transmitted). However, using a case-control design a significant increase (Likelihood ratio = 3.935, P = 0.047) in the valine allele was observed in the group of schizophrenic patients (N = 276) compared to an ethnically matched control group (N = 77). The association was stronger in female patients (P = 0.012) similar to other studies showing that some COMT behavioral effects are gender sensitive. In summary, by case-control design but not by a family-based study, there is a weak effect in female patients of the high activity COMT allele in conferring risk for schizophrenia.
儿茶酚-O-甲基转移酶（COMT）是一种广泛存在的酶，对儿茶酚代谢至关重要。COMT热稳定性的分子基础导致酶活性存在三到四倍的差异，这是由于Val158/108Met多态性中缬氨酸被甲硫氨酸替代所致。特别值得关注的是该基因在主要精神疾病中的作用，尤其是因为一个包含COMT基因的微缺失（22q11）（心脏颜面综合征）也伴有多种行为障碍，包括精神分裂症患病率增加。近20项基因研究探讨了COMT在精神分裂症中的作用，但结果不明确。为了阐明这种多态性在赋予精神病风险方面的作用，我们使用病例对照研究和基于家系的研究，对一大组文化和种族相近的巴勒斯坦阿拉伯精神分裂症三联体（N = 276）进行了研究。在194个具有至少一个杂合子亲本的信息丰富的三联体中，该样本中未观察到COMT等位基因的优先传递（传递不平衡检验统计量卡方 = 0.14，无显著性差异；131个COMT缬氨酸等位基因被传递，125个未被传递）。然而，采用病例对照设计，与种族匹配的对照组（N = 77）相比，在精神分裂症患者组（N = 276）中观察到缬氨酸等位基因显著增加（似然比 = 3.935，P = 0.047）。女性患者中的关联更强（P = 0.012），这与其他研究结果相似，表明COMT的一些行为效应具有性别敏感性。总之，通过病例对照设计而非基于家系的研究，高活性COMT等位基因在女性患者中对精神分裂症风险的影响较弱。
