Kim Jung Jin, Shirts Brian H, Dayal Madhulika, Bacanu Silviu-Alin, Wood Joel, Xie Weiting, Zhang Xiaohua, Chowdari Kodavali V, Yolken Robert, Devlin Bernie, Nimgaonkar Vishwajit L
Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania 15213, USA.
Ann Med. 2007;39(2):145-53. doi: 10.1080/07853890601083808.
Published data support genetic variants, as well as certain infectious agents, as potential risk factors for schizophrenia. Less is known about interactions between the risk factors.
To evaluate exposure to infectious agents and host genetic variation as joint risk factors.
We investigated four infectious agents: cytomegalovirus (CMV), herpes simplex viruses 1 and 2 (HSV1, HSV2), and Toxoplasma gondii (TOX). We initially compared exposure using specific serum antibodies, among simplex and multiplex nuclear families (one or more than one affected offspring, respectively). If interactions between infectious agents and host genetic variation are important risk factors for schizophrenia, we reasoned that they would be more prominent among multiplex versus simplex families. We also evaluated the role of variation at chromosome 6p21-p23 in conjunction with exposure. We used 22 short tandem repeat polymorphisms (STRPs) dispersed across this region.
Though exposure to all four agents was increased among multiplex families versus simplex families, the difference was consistently significant only for CMV (odds of exposure to CMV in multiplex families: 2.47, 95% CI: 1.48-5.33). Transmission disequilibrium tests and case-control comparisons using STRPs revealed significant linkage/association with D6S2672 among CMV+ schizophrenia patients.
Polymorphisms near D6S2672 could confer risk for schizophrenia in conjunction with CMV exposure.
已发表的数据支持基因变异以及某些感染因子是精神分裂症的潜在风险因素。对于这些风险因素之间的相互作用了解较少。
评估感染因子暴露与宿主基因变异作为联合风险因素。
我们调查了四种感染因子:巨细胞病毒(CMV)、单纯疱疹病毒1型和2型(HSV1、HSV2)以及弓形虫(TOX)。我们最初在单重和多重核心家庭(分别为有一个或多个患病后代)中使用特异性血清抗体比较暴露情况。如果感染因子与宿主基因变异之间的相互作用是精神分裂症的重要风险因素,我们推断在多重家庭与单重家庭中它们会更显著。我们还结合暴露情况评估了6号染色体p21 - p23区域变异的作用。我们使用了分布在该区域的22个短串联重复多态性(STRP)。
尽管多重家庭中所有四种感染因子的暴露均高于单重家庭,但差异仅在CMV方面始终具有统计学意义(多重家庭中暴露于CMV的比值比:2.47,95%置信区间:1.48 - 5.33)。使用STRP进行的传递不平衡检验和病例对照比较显示,在CMV阳性的精神分裂症患者中,与D6S2672存在显著连锁/关联。
D6S2672附近的多态性可能与CMV暴露共同导致精神分裂症风险。