BACKGROUND: Lines of evidence have suggested that the brain-derived neurotrophic factor (BDNF) gene may be involved in the pathogenesis of schizophrenia. Two common functional polymorphisms C-270T and Val66Met within the BDNF gene were first reported by Kunugi et al. [Kunugi, H., Nanko, S., Hirasawa, H., Kato, N., Nabika, T., Kobayashi, S., 2003. Brain-derived neurotrophic factor gene and schizophrenia: polymorphism screening and association analysis. Schizophr. Res. 62, 281-283.] and pls expand this too: Hong et al. (2003) to be significantly associated with schizophrenia. However, subsequently several studies obtained conflicting results. METHODS: We compared the allele/genotype frequencies of the C-270T and Val66Met polymorphisms and the haplotype frequencies at the two polymorphisms in a moderate independent patient-control sample from the Han Chinese population. Two systematic meta-analyses were performed to assess the collective evidence for association across studies for each of the two polymorphisms. RESULTS: No statistically significant differences were found in allele or genotype or haplotype frequencies between patient and normal control subjects for either of the two polymorphisms. On the other hand, the meta-analysis of all published population-based association studies showed statistically significant evidence for heterogeneity among each of the two polymorphisms. Stratification of the studies by ethnicity of the samples yielded no significant evidence for an association with the polymorphisms in the Caucasian population (for C-270T polymorphism: pooled OR(Caucasian)=0.736, 95% CI=0.476-1.139, p=0.169; for Val66Met polymorphism: pooled OR(Caucasian)=1.027, 95% CI=0.796-1.325, p=0.835), nor in the Asian population (for C-270T polymorphism: pooled OR(Asian)=0.445, 95% CI=0.144-1.373, p=0.159; for Val66Met polymorphism: pooled OR(Asian)=0.962, 95% CI=0.820-1.128, p=0.635). CONCLUSIONS: Our population-based study and meta-analysis demonstrate that the BDNF C-270T and Val66Met polymorphisms do not play major roles in the susceptibility to schizophrenia in either Caucasian or Asian populations. But we can not rule out the possibility that other polymorphisms with the BDNF gene are involved in the pathophysiology of schizophrenia.
BACKGROUND: Lines of evidence have suggested that the brain-derived neurotrophic factor (BDNF) gene may be involved in the pathogenesis of schizophrenia. Two common functional polymorphisms C-270T and Val66Met within the BDNF gene were first reported by Kunugi et al. [Kunugi, H., Nanko, S., Hirasawa, H., Kato, N., Nabika, T., Kobayashi, S., 2003. Brain-derived neurotrophic factor gene and schizophrenia: polymorphism screening and association analysis. Schizophr. Res. 62, 281-283.] and pls expand this too: Hong et al. (2003) to be significantly associated with schizophrenia. However, subsequently several studies obtained conflicting results. METHODS: We compared the allele/genotype frequencies of the C-270T and Val66Met polymorphisms and the haplotype frequencies at the two polymorphisms in a moderate independent patient-control sample from the Han Chinese population. Two systematic meta-analyses were performed to assess the collective evidence for association across studies for each of the two polymorphisms. RESULTS: No statistically significant differences were found in allele or genotype or haplotype frequencies between patient and normal control subjects for either of the two polymorphisms. On the other hand, the meta-analysis of all published population-based association studies showed statistically significant evidence for heterogeneity among each of the two polymorphisms. Stratification of the studies by ethnicity of the samples yielded no significant evidence for an association with the polymorphisms in the Caucasian population (for C-270T polymorphism: pooled OR(Caucasian)=0.736, 95% CI=0.476-1.139, p=0.169; for Val66Met polymorphism: pooled OR(Caucasian)=1.027, 95% CI=0.796-1.325, p=0.835), nor in the Asian population (for C-270T polymorphism: pooled OR(Asian)=0.445, 95% CI=0.144-1.373, p=0.159; for Val66Met polymorphism: pooled OR(Asian)=0.962, 95% CI=0.820-1.128, p=0.635). CONCLUSIONS: Our population-based study and meta-analysis demonstrate that the BDNFC-270T and Val66Met polymorphisms do not play major roles in the susceptibility to schizophrenia in either Caucasian or Asian populations. But we can not rule out the possibility that other polymorphisms with the BDNF gene are involved in the pathophysiology of schizophrenia.
Authors: Xiang Yang Zhang; Da Chun Chen; Mei Hong Xiu; Colin N Haile; Xingguang Luo; Ke Xu; Hui Ping Zhang; Lingjun Zuo; Zhijun Zhang; Xiangrong Zhang; Therese A Kosten; Thomas R Kosten Journal: Hum Genet Date: 2012-02-24 Impact factor: 4.132