[Association of cyclic adenosine monophosphate response element-binding protein gene and major depressive disorder].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD). METHODS: We recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed. RESULTS: No significant association with MDD was observed for SNPs rs10932201 and rs6740584 (P=0.1004 and P=0.4986). However, there was strong positive association between the rs10932201-rs6740584 haplotype and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022). CONCLUSION: The rs10932201-rs6740584 haplotype of the CREB1 gene may play an important role in the pathogenesis of MDD.

[Association between depression and G72 gene polymorphism].

OBJECTIVE: To investigate the association between G72 gene polymorphisms and depression,and to probe the difference of G72 gene polymorphisms between depression with and without mixed family history. METHODS: The polymorphisms of G72 gene (rs947267 and rs2181953) were detected by PCR technique in 100 depressive patients without mixed family history, 50 depressive patients with mixed family history and 86 normal controls. RESULTS: (1) The frequencies of rs947267 genotypes and alleles in female depressive patients without mixed family history were significant different to the controls (P=0.017 and P=0.008), the OR scores were 0.300 (A/A, P=0.010), 0.456(A, P=0.008) and 2.195(C, P=0.008) respectively; but in male patients there were no significant differences to the controls (P>0.05). (2) The frequencies of rs2181953 genotypes and alleles in the depressive patients without mixed family history were not significantly different to the controls regardless of sex (P>0.05). (3) The frequencies of rs947267 and rs2181953 genotypes and alleles in the depressive patients with mixed family history were not significantly different to the controls regardless of sex (P>0.05). CONCLUSION: The G72 gene polymorphism may be associated with female depressive patients without mixed family history,C allele of rs947267 may be the risk factor.

[Expression levels of APP and PS1 genes in patients with Alzheimer's disease].

The gene expression levels of amyloid precursor protein (APP) and presenilin 1 (PS1) in the peripheral blood samples of patients with Alzheimer's disease(AD) and their association with the disease were studied. The absolute expression levels of APP and PS1 genes were quantified in 45 AD patients, 25 patients with vascular dementia (VD) and 60 healthy controls by real-time quantitative PCR using SYBR Green I. The APP expression levels in healthy controls, AD cases and VD cases are 0.026+/-0.005, 0.044+/-0.006 and 0.072+/-0.013 amol/microg cDNA, respectively; and the PS1 expression levels are 0.026+/-0.004, 0.051+/-0.011 and 0.039+/-0.005 amol/microg cDNA, respectively. Both APP and PS1 expression levels were significantly elevated in AD or in VD cases (APP, AD vs Control, t=2.639, P<0.01, VD vs Control, t=3.028P<0.01; PS1, AD vs Control, t=2.173P<0.05, VD vs Control, t=2.012P<0.05). It seems that elevated APP and PS1 gene expression is associated with dementia but not especially with AD.

[Genome-wide search for linkage to attention deficit hyperactivity disorder (ADHD) on the X chromosome].

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral. Boys are more often affected than girls. Family, twin and adoption studies have supported a strong genetic basis. The etiology of this disorder is not clear. Molecular genetic and pharmacological studies suggest the involvement of dopaminergic and noradrenergic neurotransmitter systems in ADHD, e.g , Several reports have found association between ADHD and the dopamine receptor gene DRD-4.the dopamine transporter gene DAT1, and the catechol-o-methyltransferase. Our previous studies showed an association between ADHD and the DXS7 locus, which is located in closely linked to the MAO gene, and MAOA gene on chromosome X. To test this hypothesis, we used the genome scan for a predisposing locus on chromosome X to ADHD. We used the tramsmission/disequilibrium test (TDT) to test for linkage between a VNTR polymorphism at the 48 markers of chromosome X and DSM-III-R oliagnosed ADHD in 84 nuclear families of the Chinese population. The TDT analysis revealed linkage between ADHD and the DXS1214(TDT: Chi2=18.1, df=7, P<0.01), DXS8102(TDT: Chi2=7.9, df=3, P<0.05), DXS1068(TDT: Chi2=21.9, df=9, P<0.01), DXS8015(TDT: Chi2=14.6, df=7, P<0.05), DXS1059(TDT: Chi2=27.8, df=10, P<0.01) and DXS8088(TDT: Chi2=20.4, df=3, P<0.01).The data showed that susceptibility loci might reside in chromosome Xp11.4-Xp21 and Xq23 for ADHD.

No association between attention-deficit hyperactivity disorder and catechol-O-methyltransferase gene in Chinese.

Previous studies suggested that the catecholaminergic systems may be involved in the pathogenesis of attention-deficit hyperactivity disorder(ADHD). Since catechel-O-methyltransferase (COMT) is an enzyme involved in the degradation of catecholaminergic neurotransmitters of the dopaminergic and noradrenergic systems,it is possible that COMT may play a role in ADHD. To test this hypothesis, we used two family-based analyses,the transmission disequilibrium test (TDT) and the haplotype-based haplotype relative risk (HHRR), to examine the possible association between COMT gene and DSM-IV-diagnosed ADHD in a Chinese sample consisting of 79 ADHD probands and their parents. Both TDT (chi2 = 1.03, df=1, P > 0.05) and HHRR (chi2 = 1.08, df = 1, P > 0.05) analyses failed to detect preferential transmission of a COMT allele to the ADHD children. Our data suggested that there was no association between ADHD and the COMT gene in the Chinese population.

102T/C SNP in the 5-hydroxytryptamine receptor 2A (HTR2A) gene and schizophrenia in two southern Han Chinese populations: lack of association.

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter that occupies a uniquely important place in neurobiology because of its role in many physiologic processes such as sleep, appetite, thermoregulation, pain perception, hormone secretion, and sexual behavior. Serotonin dysfunction has been implicated in the pathogenesis of schizophrenia. Previous studies have shown an association between the T102C polymorphism of the 5-hydroxytryptamine receptor 2A (HTR2A) gene and schizophrenia. However, many negative findings have also been reported. We analyzed the T102C polymorphism of HTR2A of schizophrenic patients in two southern Chinese populations (n = 291) and matched controls (n = 307). No significant positive association was observed between either of the polymorphisms and all schizophrenics, nor was the polymorphisms and any population of schizophrenia. These data did not provide evidence for a contribution of the 102T/C SNP of HTR2A gene to susceptibility to the southern Han Chinese schizophrenia.

[A study on the relation between the apolipoprotein E promoter -427C/T polymorphism and Alzheimer's disease].

OBJECTIVE: To determine the relation between the apolipoprotein E(apoE) promoter -427C/T polymorphism and Alzheimer's disease (AD) in a Chinese Han population in Shanghai. METHODS: The apoE promoter -427C/T polymorphism in 104 AD cases and 110 healthy subjects was detected using polymerase chain reaction method and restriction fragment length polymorphism genotyping technique. The differences in polymorphic distribution between the two groups were tested, and odds ratio was computed. RESULTS: No differences in apoE -427C/T genotypic distribution were observed between AD cases and controls (P>0.05). Even after stratification according to apoE epsilon 4 stratum, there was not any polymorphic distribution difference when epsilon 4 carriers or non epsilon 4 carriers were compared with controls (P>0.05). The association between AD and apoE epsilon 4 appeared in the TT group(OR=3.94,95%, CI:22067038, chi-square=21.48, P<0.05), but not in CT or CC group. CONCLUSION: ApoE -427C/T polymorphism was not a susceptibility factor for AD in this Han population in Shanghai.

[Associations between six functional genes and schizophrenia].

OBJECTIVE: To assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1). METHODS: With the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population. RESULTS: (1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05). CONCLUSION: The 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.

[Expression variation and mutation analysis of exon 9 and 10 in amyloid precursor protein gene in Alzheimer's disease].

To explore the expression differences of exon 9 and 10 in Amyloid Precursor Protein gene(APP9 approximately 10) in Alzheimer's disease,and detect the probable point mutation appeared in cDNA fragment of APP9 approximately 10 in the Shanghai Han people.semi-quantitative competitive RT-PCR technique was performed to detect the expression of APP9 approximately 10 in peripheral lymphocyte, and the Apolipoprotein E gene(ApoE) and Presenilin 1(PS1)gene were genotyped with PCR-RFLP method. We also analyzed the point mutation in APP9 approximately 10 cDNA through the denatured gel electrophoresis. The results are as follows:1. While compared with healthy controls,expression of APP9 approximately 10 mRNA was significantly enhanced in Alzheimer disease; 2.APOE*epsilon4 allele, the most common genetic risk factor for AD, did not affect the Expression of APP9 approximately 10 mRNA, whereas the APP9 approximately 10 mRNA expression might be increased by the allele 1 of PS1 gene, another probable susceptibility gene of AD.3. No point mutation in APP9 approximately 10 cDNA was detected. In our samples, the expression of APP9 approximately 10 mRNA in AD was significantly different from that of controls, suggesting that the change of peripheral APP9 approximately 10 mRNA expression might be another bio-marker used in clinical diagnosis for AD.