Functional variants of the genes involved in neurodevelopment and susceptibility to schizophrenia in an Armenian population

Aberrant neurodevelopment contributes to the etiology of schizophrenia. This study aimed to investigate the potential association of netrin G1 (NTNG1) rs628117 and brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) genetic polymorphisms with susceptibility to schizophrenia. One hundred three Armenian patients with schizophrenia and 105 healthy control subjects were genotyped by polymerase chain reaction with sequence-specific primers. Whereas the NTNG1 rs628117 genotypes were equally distributed in the groups, the carriers of the less common BDNF 66Met allele were overrepresented among patients with schizophrenia when compared with healthy controls (55% vs 35%, odds ratio = 2.28, 95% confidence interval 1.14-1.98, p(corrected) = 0.006). Furthermore, the 66Met/Met genotype correlated with earlier disease onset (p = 0.024). In conclusion, our single-cohort study nominates the BDNF 66Met allele as a risk factor for schizophrenia in an Armenian population. This must be confirmed in other Armenian cohorts.     

Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder

BACKGROUND: A long-term controversy exists on whether or not major psychotic disorders can be discretely divided into two groups, for example, schizophrenia and bipolar disorder. Many genes and polymorphisms have been studied for a role in both disorders, including the Val66Met (also known as rs 6265 or G196A) variant of brain-derived neurotrophic factor (BDNF). Many case-control association studies have been performed to see if BDNF could serve as a useful clinical diagnostic biomarker for schizophrenia or bipolar disorder, but results have been equivocal. OBJECTIVE: To determine, by meta-analysis, if the Val66Met polymorphism of BDNF influences risk for either schizophrenia, bipolar disorder, or both. METHODS: We searched Pubmed, Medline, and PsycInfo using keywords including Val66Met, Rs6265, G196A, BDNF, schizophrenia, and bipolar disorder. A total of 13 studies for schizophrenia and 11 studies for bipolar disorder were combined by random-effects meta-analysis. MAIN RESULTS: The pooled results from the schizophrenia sample (2955 patients; 4035 controls) and the bipolar disorder sample (3143 patients; 6347 controls) indicated lack of significance with either of the two psychoses, with pooled odds ratios of 1.00 (P=0.944) and 0.95 (P=0.161), respectively. CONCLUSION: Although there are some limitations on the study, our results indicate there is a lack of association between the Val66Met polymorphism and either of the two psychoses. A larger sample size, and evaluation of more single-nucleotide polymorphisms are needed to obtain more robust and conclusive findings regarding the relationship between the BDNF gene and psychosis.     

BDNF and HSP gene polymorphisms and their influence on the progression of primary open-angle glaucoma in a Polish population

Introduction

Glaucoma is a neurodegenerative disease that is often associated with high intraocular pressure (IOP). One of the effects of elevated IOP is disorder of neurotrophic molecules transport, including brain-derived neurotrophic factor (BDNF) and recruit specific cellular proteins called “heat shock proteins” (HSPs). The aim of this study was to evaluate a relationship between the BDNF and HSP70-1 gene polymorphisms with risk occurrence of primary open-angle glaucoma (POAG).

Material and methods

The study consisted of 167 patients with POAG (mean age: 73 ±9) and 193 healthy subjects (mean age: 64 ±13). Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP, using the following restriction enzymes: NlaIII (rs6265) and BsrBI (rs1043618). The Heidelberg retinal tomography (HRT) clinical parameters were also analyzed. The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated.

Results

Comparison of the distributions of genotypes and alleles of the 196G/A polymorphism of the BDNF gene as well as 190G/C polymorphism of the HSP70-1 gene and analysis of the odds ratio (OR) showed no statistically significant differences between POAG patients and controls (p > 0.05). However, there was a statistically significant association of the 196G/A of BDNF and 190G/C of HSP70-1 gene polymorphisms with progression of POAG depending on values of clinical parameters. 196G/A of BDNF correlated with the parameters GDx and RA (p = 0.03; p = 0.002, respectively), while 190G/C of HSP70-1 correlated with c/d and RA (p = 0.014, p = 0.024, respectively).

Conclusions

The BDNF 196G/A and HSP70-1 190G/C gene polymorphisms may be related to progression of POAG.     

Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan.

Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C > T (C270T named formerly) in the noncoding region of exon V and 196G > A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP) abuse in Japan. No significant differences were found in the frequency of the genotype or allele in these two SNPs between MAP abusers and controls (132C > T in exon V: genotype, P = 0.586, allele, P = 0.594; 196G > A (val66met) in exon XIIIA: genotype, P = 0.889, allele, P = 0.713). Furthermore, there was no difference between clinical parameters (e.g., prognosis psychosis, spontaneous relapse, or poly-substance abuse) and the two SNPs of BDNF gene. These results suggest that the two SNPs (132C > T in exon V and 196G > A (val66met) in exon XIIIA) of the BDNF gene may not be associated with Japanese MAP abusers. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.     

Genetic variants in the BDNF gene and therapeutic response to risperidone in schizophrenia patients: a pharmacogenetic study

Risperidone is a widely used atypical antipsychotic agent that produces considerable interindividual differences in patient response. We investigated the pharmacogenetic relationship between the brain-derived neurotrophic factor (BDNF) gene and response to risperidone in 127 Han Chinese schizophrenic patients. Three functional polymorphisms, (GT)_n dinucleotide repeat polymorphism, C-270T, and the rs6265G/A single-nucleotide polymorphism (SNP), were genotyped and analyzed for association, with reduction of Brief Psychiatric Rating Scale (BPRS) scores following an 8-week period of risperidone monotherapy. For individual polymorphic analysis, we found that the frequency of the 230-bp allele of the (GT)_n polymorphism was much higher in responders (47.95%) than in nonresponders (32.41%) and the difference was statistically significant even after Bonferroni''s adjustment (for the 230-bp allele: adjusted P=0.039). For haplotype-based analyses of the three polymorphisms, no positive finding was observed in the global test, but in specific haplotype tests, two haplotypes were also significantly related to response to risperidone (for haplotype 230-bp/C-270/rs6265G: P=0.0009; for haplotype 234-bp/C-270/rs6265A: P=0.043), indicating that patients with the 230-bp allele of the (GT)_n polymorphism or the 230-bp/C-270/rs6265G haplotype responded better to risperidone than those with other alleles or haplotypes, and that the positive effect of the individual haplotype 230-bp/C-270/rs6265G was mainly driven by the 230-bp allele. These findings demonstrate that the individual and combinatorial genetic variants in the BDNF gene might have a role in the therapeutic response to risperidone in the Han Chinese population.     

Polymorphisms of brain-derived neurotrophic factor associated with heroin dependence

Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. It also plays a role in the reward response to many drugs, including heroin. To identify genetic variants associated with heroin dependence, we compared four single nucleotide polymorphisms (SNPs, rs13306221, rs6265, rs56164415, and rs16917204) of the BDNF gene in 487 subjects with heroin dependence and 492 healthy individuals. The analysis revealed the G allele of rs6265 was significantly more common in heroin-dependent subjects than in the healthy controls (P=0.001 after Bonferroni correction). Among heroin-dependent individuals, the onset of dependence was significantly earlier in individuals with GG or GA genotypes compared to AA individuals (P<0.01). Additionally, we found that the G allele of rs13306221 was significantly more frequent in heroin-dependent subjects than in controls (P=0.005 after Bonferroni correction). These findings support a role of BDNF rs6265 and rs13306221 polymorphisms in heroin dependence and may guide future studies to identify other genetic risk factors for heroin dependence.     

The IL18 gene and Hashimoto thyroiditis in children

Interleukin 18 (IL18) stimulates interferon-γ production in Th1 cells which are prominent in the thyroid of Hashimoto thyroiditis (HT). We investigated the association between the IL18 gene and HT. There were 116 children with HT and 1272 controls. rs187238 and rs1946518 in the promoter region of the IL18 gene were genotyped. Differences in genotype, allele, carrier, and haplotype distributions between patients and controls were compared. A Pc value <0.05 was considered significant. The frequency of the C/G genotype of rs187238 was significantly higher in patients and conferred a risk of HT (OR, 1.96; 95% CI, 1.30–2.95; Pc, 0.0021). So did the frequencies of allele C (OR, 1.73; 95% CI, 1.22–2.44; Pc, 0.0035) and carrier C (OR, 1.96; 95% CI, 1.31–2.92; Pc, 0.0017), however the frequency of the G/G genotype was significantly lower in patients than in controls (OR, 0.51; 95% CI, 0.34–0.76; Pc, 0.0034). There was no association between HT and rs1946518. The CT haplotype was significantly more frequent in patients than in controls and conferred a risk of HT (OR, 1.76; 95% CI, 1.24–2.49; Pc, 0.0049). We concluded that the IL18 gene was associated with HT in children. The rs187238C allele and CT haplotype conferred a risk of HT.     

Investigation of the effect of brain-derived neurotrophic factor (BDNF) polymorphisms on the risk of late-onset Alzheimer's disease (AD) and quantitative measures of AD progression

BDNF is a functional candidate gene for AD, owing to its role in neuronal development and survival. The Val66Met (G196A), along with another C270T polymorphism has been associated with AD, however, the effects seem to be inconsistent across studies. We examined the association of the G196A and C270T polymorphisms with sporadic late-onset AD (LOAD) in a large American White cohort of 995 AD cases and 671 controls and an American Black cohort of 64 AD cases and 45 controls. We also examined the association of these polymorphisms with quantitative measures of AD progression, including age at onset (AAO), disease duration and Mini-Mental State Examination (MMSE) scores. No significant difference in allele, genotype or estimated haplotype frequencies was observed between AD cases and controls within the American White and Black cohorts for the G196A and C270T polymorphisms. However, the frequency of the 196*A allele was significantly lower in American Black subjects compared to Whites. While MMSE scores were significantly lower in C270T/CT carriers compared to C270T/CC subjects only among American Blacks, no such effect was observed among American Whites. The BDNF polymorphisms did not affect AAO or disease duration measures in American Whites or Blacks. Our finding does not support any association between the BDNF/G196A or C270T polymorphism and the risk of sporadic LOAD among American Whites or Blacks. The significant effect of the C270T polymorphism observed on MMSE scores among American Blacks needs to be further explored in a larger cohort.     

Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor

To investigate the association of the rs6265 (Val66Met) single nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) with brain morphometry and functional status as measured by quantitative magnetic resonance imaging (MRI) and neurocognitive testing in multiple sclerosis (MS) patients. BDNF is released by neurons and by immune cells in MS brain. The rs6265 SNP variation of BDNF causes substitution of valine (Val) for methionine (Met) and interferes with activity-dependent BDNF secretion. A total of 209 treated MS patients (161 females; 48 males) underwent clinical brain MRI and were genotyped for the BDNF rs6265 Val66Met SNP. A subset of 108 patients had neurocognitive testing for processing speed, memory and executive function. The MRI measurements included T2 and T1-lesion volume (LV); normalized brain volume measures of whole brain (WB) volume, white and gray matter volume (NWMV and NGMV) and the diffusion-weighted imaging measure of WB mean parenchyma diffusivity (MPD). The Met66 allele status was positively associated with NGMV (P = 0.015, standardized beta = 0.15) and negatively associated with T2-LV (P = 0.041, standardized beta = -0.14). There were no significant associations between Met66 allele status and T1-LV, NWMV or MPD. On the Paced Serial Addition Test (PASAT), a trend (P = 0.057) favoring the Met66 allele group was observed. There were no significant associations between Met66 allele status and other neurocognitive measures. The BDNF Met66 allele is associated with lower damage as evidenced by measurement of NGMV and T2-LV in MS patients.     

Association study of neuregulin 1 gene polymorphisms with auditory P300 in schizophrenia

Neuregulin 1 (NRG1), a gene involved with myelin production has been shown to have a positive correlation with schizophrenia. Event-related potentials (ERPs) studies provide the evidence of disturbed electrophysiologic marker in schizophrenia. The present study investigated the association of NRG1 genotypes with P300 in schizophrenia. Three polymorphisms in NRG1 gene were detected in 287 Chinese Han schizophrenics and 120 healthy control subjects. Among the total sample, 140 patients and 96 controls underwent P300. There were no significant differences for genotype distributions and allele frequencies between schizophrenic group and the control. A significant difference was observed between the schizophrenic patients and controls in the AT haplotype, with Odds Ratio 0.304 (P = 0.000882, 95% CI = 0.145-0.636). P300 amplitude in the schizophrenic group was significantly lower than that of the controls at Fz, Cz, Pz. P300 latency in the schizophrenic group was also significantly longer than that of the controls at Cz, Pz, Fz. Significant differences of P300 latency between three genotypes of rs3924999 were found at Cz and Pz both in schizophrenic group and the controls. The G/G carriers of rs3924999 tended to perform worse in the P300 latency as compared to A/A or A/G carriers both in the schizophrenia and controls. There were no significant differences for P300 latency and amplitude between schizophrenic group and controls for AT haplotype. NRG1 gene is a susceptible gene for Chinese Han schizophrenia and AT haplotype might have the protective role in the schizophrenia. Rs3924999 in NRG1 gene might functionally impact cognitive processing.     

Polymorphisms of the Homologous Recombination Gene RAD51 in Keratoconus and Fuchs Endothelial Corneal Dystrophy

Purpose. We investigated the association between genotypes and haplotypes of the c.-61G>T (rs 1801320) and c.-98G>C (rs 1801321) polymorphisms of the RAD51 gene and the occurrence of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) in dependence on some environmental factors. Methods. The polymorphisms were genotyped in peripheral blood lymphocytes of 100 KC and 100 FECD patients as well as 150 controls with PCR-RFLP. Results. The G/T genotype of the c.-61G>T polymorphism was associated with significantly increased frequency occurrence of KC (crude OR 2.99, 95% CI 1.75–5.13). On the other hand, the G/G genotype of this polymorphism was positively correlated with a decreased occurrence of this disease (crude OR 0.52, 95% CI 0.31–0.88). We did not find any correlation between genotypes/alleles of the c.-98G>C polymorphism and the occurrence of KC. We also found that the G/G genotype and G allele of the c.-98G>C polymorphism had a protective effect against FECD (crude OR 0.51, 95% CI 0.28–0.92; crude OR 0.53, 95% CI 0.30–0.92, resp.), while the G/C genotype and the C allele increased FECD occurrence (crude OR 1.85, 95% CI 1.01–3.36; crude OR 1.90, 95% CI 1.09–3.29, resp.). Conclusions. The c.-61T/T and c.-98G>C polymorphisms of the RAD51 gene may have a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.     

Transmission distortion of BDNF variants to bipolar disorder type I patients from a South American population isolate.

Recent reports have implicated polymorphisms in the brain derived neurotrophic factor (BDNF) gene region in the etiology of several psychiatric phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of BDNF (Val66Met), an apparently functional variant of this key BDNF. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders.     

广西人群中IL-33 基因rs10975521A / T、rs1929992A / G 多态性的分布特点

目的：研究探讨IL-33基因rs10975521A/T、rs1929992A/G的基因多态性在广西人群中的分布特点。分析两位点的基因型及基因频率在不同种族间的分布差异。方法：采用单碱基延伸法(PCR-SEB)及DNA测序法对283例受试者IL-33基因rs10975521A/T、rs1929992A/G位点进行多态性分析。用统计学方法分析其分布频率及组间差异。结果： rs10975521A/T 存在AA、AT、TT三种基因型,分布频率分别为12.7%、53.0%、34.3%。其各基因型及等位基因频率在广西人群中男女性别之间无显著差异( P >0.05)。其等位基因频率与人类基因组计划公布的欧洲人( P <0.05)、北京汉族人( P <0.05)及日本人群( P <0.01)之间均有显著差异。rs1929992A/G存在AA、AG、GG三种基因型,分布频率分别为23.9%、53.7%、13.4%。其各基因型及等位基因频率在广西地区人群中男女之间也无统计医学意义( P >0.05)。其基因型与欧洲人( P <0.01)、北京汉族人( P <0.05)和日本人( P <0.01)之间差异有统计学意义。等位基因频率与欧洲人( P <0.01) 、北京汉族人( P <0.05) 相比差异有统计学意义。结论： IL-33基因rs10975521A/T、rs1929992A/G的基因多态性在种族和地区间存在不同程度的差异。     

广西人群IL-22基因多态性分布特征及其与血脂的关系

目的:研究广西正常人群中白细胞介素22(IL-22)基因rs2227485C/T和rs2227491A/G位点的多态性分布特点和在不同人群间的分布差异,探讨不同基因型间常见血脂指标水平的差异。方法:采取多重单碱基延伸法(SNa Pshot)和DNA测序相结合的方法对280例广西人群IL-22基因的rs2227485C/T和rs2227491A/G位点进行基因分型检测,并用统计学方法比较各组间多态性分布的差异及不同基因型间血脂指标水平的差异。结果:rs2227485C/T存在CC、CT和TT 3种基因型,分布频率分别为17.1%、49.3%和33.6%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),其基因型及等位基因与国际人类基因组单体型图计划公布的意大利、北京、日本和墨西哥人群相比,差异有统计学意义(P0.05);rs2227491A/G存在AA、AG和GG 3种基因型,分布频率分别为16.1%、52.8%和31.1%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),基因型频率与意大利、日本和墨西哥人群之间的差异有统计学意义(P0.05),等位基因分布频率与其他4个人群相比差异均有统计学意义(P0.05)。rs2227491A/G位点3种基因型间的HDL-C和LDL-C差异有统计学意义(P0.05),其中HDL-C在AG/AA与GG组比较差异有统计学意义(P0.05),LDL-C在AG/GG和AA组比较差异有统计学意义(P0.05)。结论:IL-22基因rs2227485C/T和rs2227491A/G位点多态性在不同人群间存在着差异。rs2227491A/G多态性与血脂水平相关。     

Relationship between the single nucleotide polymorphisms of β2-adrenergic receptor 5’-regulatory region and essential hypertension in Chinese Kazakh ethnic minority group

Objective: To study the correlation of β₂-AR gene 5’-regulatory region SNPs and essential hypertension (EH) in Chinese Kazakh ethnic minority group. Methods: The Sequenom MassArray^® SNP detection technology was used to detect β₂-AR gene 5’-regulatory region SNPs in 150 Xinjiang Kazakh EH patients and 150 controls. Biochemical analyzer was used to detect lipid and other related biochemical parameters. SHEsis and other software were used to analyze linkage disequilibrium and haplotype. Results: Six loci rs205304 (-1023G/A), rs17108803 (-893T/G), rs12654778 (-654G/A), rs11168070 (-468C/G), rs11959427 (-367C/T) and rs2895795 (-1429T/A) polymorphisms of β₂-AR gene 5’-regulatory region were found in the Xinjiang Kazakh populations. While, there was no significant difference between EH group and NH in genotypes and allele frequency of rs2053044, rs12654778, rs2895795, rs17108803 and rs11959427 (P>0.05). However; significant differences were detected of rs11168070 genotypes and allele frequency in two groups (P<0.05). Analysis of the linkage disequilibrium and haplotype in Kazakh population, there is a strong linkage disequilibrium of rs11168070, rs2053044, rs2895795 gene polymorphism in the EH group, and rs11168070, rs12654778, rs17108803 gene polymorphism in controls. Frequency of haplotype GTCCAT, GACTGT and ATGCGT in EH group was higher (P<0.05), while frequency of ATCTGT, ATGTGT, GTCCGT, GTCTAT, GACCAT and GTCTGT in the EH group was significantly lower than the control (P<0.05). Conclusions: β₂-AR gene 5’-regulatory region of rs11168070, rs2053044, rs17108803, rs12654778, rs11959427 and rs2895795 genetic polymorphism exists in Kazakh. Among them, rs11168070 locus genotype and allele frequency distribution in the two groups are significant differences. In six polymorphic loci, there is a strong linkage disequilibrium, which haplotypes GTCCAT, GACTGT, ATGCGT are risk factors of EH, and the ATCTGT, ATGTGT, GTCCGT, GTCTAT, GACCAT, GTCTGT are protective factors.     

Association between promoter polymorphisms in anterior pharynx-defective-1a and sporadic Alzheimer's disease in the North Chinese Han population

Amyloid β-peptide (Aβ) deposition in brain is important in the development of sporadic Alzheimer's disease (SAD) and Aβ is produced through sequential cleaving of amyloid precursor protein (APP) by β-secretase and γ-secrease. Anterior pharynx-defective-1 (APH-1) is an important subunit of the gamma-secretase complex, and its expression level was associated with the activity of γ-secrease. We hypothesized that alterations in the APH-1 promoter region might alter APH-1 expression and the activity of γ-secrease, thus be involved in the SAD process. In the present study, we sequenced APH-1a promoter region in 20 randomly selected controls and 20 SAD patients and detected two polymorphisms which were −980C/G (rs3754048) and −21C/A (rs2275780). Then, we investigated genotypes and allele of these two polymorphisms as well as apolipoprotein ?4 (APOE ?4) status in 256 SAD patients and 276 normal controls with restriction fragment length polymorphisms analysis and sequencing. Results showed the GG genotype and G allele of −980C/G polymorphism were more frequent in the SAD group than that in the controls not only in the whole subjects (genotype P = 0.038, allele P = 0.01 respectively) but also in the APOE ?4 + subjects (genotype P = 0.048, allele P = 0.016 respectively). There was no statistical difference between SAD group and controls regarding to the frequency of alleles and genotypes of −21C/A whenever before or after stratification by APOE ?4. Our results suggest that there is an association between −980C/G and the development of SAD in the Northern Han Chinese population and that allele G may interact synergistically with the APOE ?4 allele to increase the risk of SAD.     

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C–1019G, HTR2A–1438A/G, TPH1 218A/C, and TPH2–703G/T variants with schizophrenia. A total of 202 patients with schizophrenia and 165 normal controls were genotyped for HTR1A C–1019G, HTR2A–1438A/G, TPH1 218A/C, and TPH2–703G/T single nucleotide polymorphisms (SNPs). In order to assess the severity of a patient’s psychiatric symptoms, the brief psychiatric rating scale (BPRS), the positive and negative symptom scale (PANSS), and the Calgary depression scale for Schizophrenia (CDSS) were administered. Genotype and allele frequencies were compared between groups via χ² statistics. Associations between the genotypes of candidate SNPs with the severity of symptoms were examined with ANOVA by comparing the mean scores of BPRS, PANSS, and CDSS according to genotype. No significant differences in the genotype distributions and allele frequencies of four SNPs were found between patients with schizophrenia and normal controls. There was a trend towards association of HTR1A C–1019G polymorphism with negative symptom. Negative symptom score of PANSS was lower in the patients with CC genotype than in the G allele carriers. These results suggested that C allele might be associated with lesser negative symptom. More studies are needed to confirm these findings. In the future, we plan to study the associations between schizophrenia and other genetic polymorphisms.     

The brain-derived neurotrophic-factor (BDNF) val66met polymorphism is associated with geriatric depression: a meta-analysis

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with geriatric depression and age-matched controls. A total of five studies involving 523 cases with geriatric depression and 1,220 psychiatrically healthy controls was included. Met allele carriers had an increased risk for geriatric depression when compared to Val/Val homozygotes (P = 0.004, OR = 1.48, 95% CI = 1.13-1.93). Our findings suggest the BDNF Met allele may confer increased risk for depression as individual age.     

The 196G/A (val66met) polymorphism of the BDNF gene is significantly associated with binge eating behavior in women with bulimia nervosa or binge eating disorder

The brain-derived neurotrophic factor (BDNF) is involved not only in promoting neuronal outgrowth and differentiation, synaptic connectivity and neuronal repair, but also in modulating eating behavior. Since genetic factors likely contribute to the biological vulnerability to bulimia nervosa (BN) and binge eating disorder (BED), we investigated whether the functional 196G/A single nucleotide polymorphism (SNP) of the BDNF gene was associated to BN and/or BED or to some phenotypic aspects of the disordered eating. Two hundred and ten Caucasian women (126 with BN, 84 with BED and 121 healthy controls) participated into the study. No significant differences were found in the frequencies of the 196G/A variants of the BDNF gene among patients with BN or BED and healthy controls. In both BN and BED groups, subjects carrying the 196A/A genotype exhibited a weekly frequency of bingeing and a severity of binge eating (as assessed by the Bulimia Investigation Test Edinburgh) significantly higher than those with the 196A/G and 196G/G genotypes. These results suggest that the 196G/A SNP of the human BDNF gene does not contribute to the genetic susceptibility to BN and BED, but may predispose those patients to a more severe binge eating behavior.     

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.