Zintzaras Elias
Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
Psychiatr Genet. 2007 Apr;17(2):69-75. doi: 10.1097/YPG.0b013e32801119da.
To evaluate whether the G196A and C270T polymorphisms of the brain-derived neurotrophic factor gene are associated with increased risk of schizophrenia.
A meta-analysis of nine genetic association studies was carried out. The meta-analysis included genotype data on 1404/1597 schizophrenics/controls for G196A and 877/989 schizophrenics/controls for C270T.
The overall analysis for investigating the association of the G196A allele G and the risk of developing schizophrenia relative to the allele A, showed significant evidence of heterogeneity (P=0.05, I(2)=58%) between the studies and nonsignificant association [random effects odds ratio 1.08 and 95% confidence interval (0.88-1.32)]. In Caucasians, there was a trend towards heterogeneity (P=0.19, I(2)=40%), then, the random and fixed effects odds ratios were 1.24 (0.96-1.60) and 1.27 (1.06-1.53), respectively. For the C270T polymorphism, overall, there was significant evidence of heterogeneity between studies (P=0.07, I(2)=55%) and the allele T was associated with a 63% increased risk of schizophrenia compared with C allele [random effects odds ratio 1.63 (1.01-2.65)]. The dominant model for allele T produced significant association [random effects odds ratio 1.68 (1.02-2.79)]. No source of bias was seen in the selected studies and the differential magnitude of effect in large versus small studies was not significant.
The meta-analysis results provided a weak evidence of association between C270T polymorphism and schizophrenia, and large heterogeneity between studies, whereas there was no evidence of association for G196A polymorphism. The above findings reinforce the need for large and more rigorous association studies.
评估脑源性神经营养因子基因的G196A和C270T多态性是否与精神分裂症风险增加相关。
对9项基因关联研究进行荟萃分析。该荟萃分析纳入了1404/1597例精神分裂症患者/对照的G196A基因型数据以及877/989例精神分裂症患者/对照的C270T基因型数据。
关于G196A等位基因G与相对于等位基因A患精神分裂症风险的关联的总体分析显示，研究之间存在显著的异质性证据（P = 0.05，I² = 58%），且关联不显著[随机效应比值比为1.08，95%置信区间为（0.88 - 1.32）]。在白种人中，存在异质性趋势（P = 0.19，I² = 40%），随机效应和固定效应比值比分别为1.24（0.96 - 1.60）和1.27（1.06 - 1.53）。对于C270T多态性，总体而言，研究之间存在显著的异质性证据（P = 0.07，I² = 55%），与C等位基因相比，等位基因T与精神分裂症风险增加63%相关[随机效应比值比为1.63（1.01 - 2.65）]。等位基因T的显性模型产生了显著关联[随机效应比值比为1.68（1.02 - 2.79）]。在所选研究中未发现偏倚来源，且大小研究之间效应大小的差异不显著。
荟萃分析结果提供了C270T多态性与精神分裂症之间关联的微弱证据，且研究之间存在较大异质性，而G196A多态性则无关联证据。上述发现强化了进行大规模且更严谨的关联研究的必要性。
