Progress in Neuro-Psychopharmacology and Biological Psychiatry
The study of BDNF Val66Met polymorphism in Chinese schizophrenic patients
Introduction
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors, not only regulates cell survival, proliferation, and synaptic growth in the developing central nervous system (CNS), but also is a critical element in modulating synaptic changes and brain plasticity (Poo, 2001, Tyler et al., 2002, Egan et al., 2003). Converging lines of evidence suggest that BDNF could be implicated in the neurodevelopmental abnormalities found in schizophrenia brain (Nawa et al., 2000). Recent studies indicate that a single nucleotide polymorphism (rs6265) producing a nonconservative amino acid substitution (valine to methionine) in the 5′-precusor peptide (pro-BDNF) at codon 66 (Val66Met) has been shown to dramatically alter the intracellular trafficking and packaging of pro-BDNF and, thus, regulate secretion of the mature peptide (Egan et al., 2003). Two studies reported that the Val66Met polymorphism of the BDNF gene was associated with susceptibility for schizophrenia (Neves-Pereira et al., 2005, Rosa et al., 2006). However, several studies did not replicate the result (Naoe et al., 2007, Xu et al., 2007, Varnäs et al., 2008). The most recent meta-analysis results provided no evidence of association between Val66Met polymorphism and schizophrenia, and large heterogeneity between studies (Kanazawa et al., 2007, Zintzaras, 2007).
Two recent studies in Japanese (Numata et al., 2006) and African–American cohort (Chao et al., 2008) show that the BDNF Val66Met polymorphism is associated with age of onset of schizophrenia; however, other studies in Caucasian populations have not observed a similar association (Gourion et al., 2005, Naoe et al., 2007). It was thought important to replicate the work with a different ethnic population to rule out a false positive result from ethnic differences in the frequency distribution of the DNA marker or from the population structure. The present work was therefore undertaken to investigate whether the BDNF Val66Met polymorphism was associated with susceptibility for schizophrenia and onset of this disease in ethnically homogeneous samples of Chinese Han population.
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Subjects
Three hundred and eighty-seven physically healthy patients (male/female = 259/128) who met DSM-IV for schizophrenia and unrelated 365 healthy controls (255 men and 110 women) were included in the study. All schizophrenic patients were recruited from among the inpatients of Beijing Hui-Long-Guan Hospital, a Beijing City owned psychiatric hospital. Diagnoses were made for each patient by two independent experienced psychiatrists. All schizophrenic patients were of the chronic type, with duration of
Results
Table 1 shows the characteristics of the subjects in the schizophrenia and normal controls. There were no significant differences in sex, age, education and BMI between two groups (all p > 0.05). Allele frequencies, genotype distributions and the statistical analysis are shown in Table 2. Genotype distributions had no deviation from Hardy–Weinberg equilibrium in both groups (p > 0.05). There was no significant difference in frequency of alleles of BDNF in schizophrenia and normal controls (χ2 = 0.09,
Discussion
Our results demonstrate that the BDNF Val66Met polymorphism may not contribute directly to the susceptibility to schizophrenia. This polymorphism however is associated with age of onset of schizophrenia, which is consistent with two previous studies in Japanese (Numata et al., 2006) and African–American cohort (Chao et al., 2008), although some other studies have not found a similar association in Caucasian population (Gourion et al., 2005, Naoe et al., 2007). Thus, the association between the
Acknowledgments
This study was supported by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education, and Clinical Center, United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639.
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These three authors (Dong Hao Zhou, Quan Zhi Yan, and Xiao Mei Yan) contributed equally to the study.