Disorder In Chinese Han Population Research Articles

A Genetic Family Cohort Study of Bipolar Disorder in Chinese Han Population

A Genetic Family Cohort Study of Bipolar Disorder in Chinese Han Population

Increased Serum C3 and Decreased UA in Patients of Bipolar Disorder in Chinese Han Population.

The aim of this study is to explore the changes and clinical significance of serum C3, C4, hypersensitive C-reactive protein (hsCRP) and uric acid (UA) in patients of bipolar disorder (BD). In this case-control study, we recruited 141 BD patients from The Second Xiangya Hospital, Central South University, and 151 age and gender matched healthy controls (HC) from the health management central of The Second Xiangya Hospital. These patients were divided into two subgroups based on medicines use: 91 patients were treated with psychiatric drugs and 50 patients were drugs free, or four subgroups based on mood states: 54 patients in manic/hypomanic phase, 30 patients in depressive phase, 52 patients in euthymic phase and 5 patients in mixed phase. Serum levels of C3, C4, hsCRP and UA were measured in all subjects. The serum C3 levels in BD patients (0.9981 ± 0.1849 g/L) were significantly lower than that in HC group (1.0637 ± 0.2186 g/L), especially the drugs free subgroup and the euthymic subgroup (0.975 ± 0.153 and 0.983 ± 0.182 g/L), while the serum UA levels were significantly higher (354.6 ± 90.4 vs. 332.9 ± 88.7 μmol/L), especially the drug-treated subgroup and manic/hypomanic subgroup (361.56 ± 93.20 and 376.70 ± 88.89 μmol/L), and rates of hyperuricaemia (31.91 vs. 17.88%) were significantly higher in BD patients than in HC group. The serum C4 and hsCRP levels in HC group showed no significant difference with BD patients in whole or those subgroups. These findings suggested that the complement and purinergic systems of BD patients might be disrupted, the UA levels could be a potential marker in manic phase and the C3 might be the marker of therapeutic evaluation of BD patients.

Methylation Status of the Serotonin Transporter Promoter CpG Island Is Associated With Major Depressive Disorder in Chinese Han Population: A Case-Control Study.

This study was aimed to investigate the relationship between the methylation status of serotonin transporter (5-HTT) and major depressive disorder (MDD) in Chinese Han population. A total of 96 patients with MDD and 55 healthy volunteers were recruited, and the methylation index (MtI) at six positions in the cytosine-phosphate-guanosine island of 5-HTT gene was measured for each subject using bisulfite pyrosequencing. MtIs at positions 5 and 6 were higher in patients with MDD than those in controls. According to the multivariable logistic regression analysis, MtIs at positions 4 and 5 were significantly associated with MDD. Besides, depression education was an independent risk factor, whereas higher educational levels were protective factors for MDD. In addition, positions 1 and 4 were negatively correlated with weight and diurnal variation. Therefore, 5-HTT methylation might be closely related with MDD in Chinese Han population because of the correlation with diurnal variation and weight.

An association study of the m6A genes with major depressive disorder in Chinese Han population

BackgroundMajor depressive disorder (MDD) is a common, chronic and recurrent mental disease but the precise mechanism behind this disorder remains unknown. FTO is one of the N6-methyladenosine (m6A) modification genes and has recently been found to be associated with depression. N6-methyladenosine (m6A) is the most abundant internal modification on RNA, which is highly enriched within the brain. There are five genes involved in m6A modification including FTO, but whether these m6A modification genes could confer a risk of MDD is still unclear. This study aimed to investigate the genetic influence of the m6A modification genes on risk of MDD. MethodsWe genotyped 23 SNPs in 5 modification genes among 738 patients with MDD and 1098 controls. The UNPHASED program was applied to analyze the genotyping data for allelic and genotypic association with MDD. ResultsOf the 23 SNPs selected, rs12936694 from the m6A demethylase gene ALKBH5 showed allelic association (χ2=11.19, p=0.0008, OR=1.491, 95%CI 1.179–1.887) and genotypic association (χ2=12.26, df=2, p=0.0022) with MDD. LimitationsReplication and functional study are required to draw a firm conclusion. ConclusionsThe ALKBH5 gene may play a role in conferring risk of MDD in the Chinese population.

Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han population

To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population. Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software. Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms. Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.

Association analysis of COMT/MTHFR polymorphisms and major depressive disorder in Chinese Han population

BackgroundIn several previous biochemical and genetic studies, the Val158Met polymorphism of the gene encoding catechol-O-methyltransferase (COMT) and the C677T polymorphism of Methylenetetrahydrofolate reductase (MTHFR) have been suggested to be involved in the pathogenesis as well as the treatment response of major depressive disorder (MDD), but the results have been inconsistent. In this study, we investigate the association of COMT/MTHFR and their interactions with MDD and antidepressant response in Chinese Han population. MethodsThree hundred and sixty eight depressed patients who met DSM-IV criteria for MDD were recruited for the study. Two hundred and nineteen normal controls were recruited from the local community. Patients and normal controls were genotyped for the functional COMT val158met and MTHFR C677T polymorphisms. Patients were characterized for clinical response to antidepressant treatment as measured by intra-individual changes of Hamilton Depression (HAMD-17) scores over 6 weeks. ResultsThe T allele (OR=1.81; CI95%=1.40–2.34, P<0.001) and C/T genotype (OR=3.66; CI95% =2.53–5.28, P<0.001) of MTHFR C677T were significantly different between case and control groups. The COMT Met/Val genotype was more common among depressed individuals than among controls (OR=1.52, CI95%=1.04–2.21, P=0.02). LimitationThere is disequilibrium in age and sex between case and control groups. Though we control the two variables in the statistic analysis, to be more accurate, we need to increase sample size in further study. ConclusionIndividuals with the genotype COMT Met/Val and MTHFR C/T have more probability of suffering from MDD. However, there is no association between gene polymorphism and treatment response.

Involvement of tryptophan hydroxylase 2 gene polymorphisms in susceptibility to tic disorder in Chinese Han population

BackgroundTryptophan hydroxylase-2 (TPH2) is a potential candidate gene for screening tic disorder (TD).MethodsA case–control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs) of the TPH2 gene in 149 TD children and in 125 normal controls.ResultsFor rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR) =3.077, 95% confidence interval (CI): 1.273–7.437; P = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153–9.040; P = 0.020). The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS) than those in controls among the male children (OR = 1.684, 95%: 1.097–2.583; P = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139–9.513; P = 0.022). We also found that genotype distributions of both SNPs were different between the Asian and European populations.ConclusionsOur results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD),these findings need to be confirmed by studies in much larger samples.

Polymorphisms and Haplotypes in theYWHAEGene Increase Susceptibility to Bipolar Disorder in Chinese Han Population

Schizophrenia and bipolar disorder are 2 major psychiatric illnesses sharing some specific genetic risk factors. Increasing evidence suggests the 2 illnesses might be more closely related than previously considered. To test this hypothesis, we investigated the allele and genotype frequencies of 11 single nucleotide polymorphisms (SNPs) and the haplotypes in these SNPs of the YWHAE gene. 1,982 patients were interviewed by 2 independent, experienced psychiatrists. Bipolar disorder diagnoses were made in strict accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria using the Structured Clinical Interview for DSM-IV Axis I Disorders. In 2011, we conducted this genetic association analysis between 11 SNPs in YWHAE and bipolar disorder, involving a male group and a female group. In the analysis of allele and genotype frequencies, the SNP rs1873827 increased susceptibility to bipolar disorder in the male group. The haplotype analysis of CAC in rs3752826, rs2131431, and rs1873827 in the male group (χ2 = 25.744, P = 3.97E-07, OR = 0.478 [95% CI, 0.358-0.639]) and of ACT and CAC in rs3752826, rs2131431, and rs1873827 in the female group (for ACT, χ2 = 30.365, P = 3.67E-08, OR = 0.040 [95% CI, 0.007-0.218]; for CAC, χ2 = 16.874, P = 4.04E-05, OR = 0.597 [95% CI, 0.466-0.765]) showed they are protective factors for bipolar disorder. However, the haplotype analysis of CAT in the male group (χ2 = 19.874, P = 8.39E-06, OR = 2.314 [95% CI, 1.587-3.374]) and of AAC and CAT in the female group (for AAC, χ2 = 38.561, P = 5.47E-10, OR = 7.104 [95% CI, 3.471-14.540]; for CAT, χ2 = 25.497, P = 4.52E-07, OR = 2.076 [95% CI, 1.556-2.770]) showed they are risk factors for bipolar disorder. Considering the size of our sample, the results suggest that YWHAE does play a major role in bipolar disorder in the Han Chinese population.

Lack of association between polymorphism -592A/C in the promoter region of IL10 gene and obsessive-compulsive disorder in Chinese Han population

Lack of association between polymorphism -592A/C in the promoter region of <i>IL10</i> gene and obsessive-compulsive disorder in Chinese Han population

Association of catechol‐O‐methyl transferase (COMT) gene −287A/G polymorphism with susceptibility to obsessive–compulsive disorder in Chinese Han population

Several studies suggested a genetic component in the etiology of obsessive-compulsive disorder (OCD). COMT involves in the degradation of dopamine and norepinephrin. As another functional SNP locus, COMT -287A/G polymorphism showed an effect on enzyme activity, suggesting that it may influence brain dopamine levels. To identify association of COMT -287A/G polymorphism with susceptibility to OCD in Chinese Han population. We evaluate the genetic contribution of the COMT -287A/G polymorphism in 200 OCD patients and 403 OCD-free control of Chinese Han population by PCR-RFLP. In addition, we investigate whether COMT -287A/G polymorphism is associated with one or more of these symptom dimensions or other characteristics such as sex, age of onset, and tic-relatedness and evaluate the association of the factorial structure of OCD symptoms from the Y-BOCS checklist with the COMT -287A/G polymorphism. A statistical difference was found in the genotypic frequencies of COMT -287A/G between the OCD and control groups (χ(2) = 13.99, DF = 2, P = 0.00091) and in the genotypic frequencies of GG genotype versus AA and AG genotypes of COMT -287 (χ(2) = 13.49, DF = 1, P = 0.00024, OR = 3.43, 95% CI = 1.78-6.62). There was a trend for an association in the genotypic distributions of COMT -287A/G polymorphism of males (χ(2) = 27.81; DF = 2; P < 0.001) and females (χ(2) = 7.31; DF = 2; P = 0.026) between the OCD patients and the controls. Using principal component analysis, we derived 5 factors from 12 main contents of OCD symptoms from the Y-BOCS checklist and found no association with COMT -287A/G polymorphism. Our study supports the involvement of the COMT -287A/G polymorphism in the genetic susceptibility to OCD in Chinese Han population.

The MDGA1 gene confers risk to schizophrenia and bipolar disorder

Objective The structural, cytoarchitectural and functional brain abnormalities reported in patients with mental disorders may be due to aberrant neuronal migration influenced by cell adhesion molecules. MDGA1, like Ig-containing cell adhesion molecules, has several cell adhesion molecule-like domains. Moreover, Kahler et al. (2008) reported that the MDGA1 gene was a schizophrenia susceptibility gene in Scandinavian population. To further investigate whether the MDGA1 gene is a shared risk factor of schizophrenia, bipolar disorder and major depressive disorder in Chinese Han population, we conducted this study. Methods We recruited 1135 unrelated schizophrenia patients, 1135 unrelated bipolar disorder patients, 1135 unrelated major depressive disorder patients and 1135 unrelated controls of Chinese Han origin. A total of eleven common SNPs were genotyped using TaqMan ® technology. Results The genotype frequency of rs11759115 differed significantly between schizophrenia patients and controls. The C-C haplotype of rs11759115-rs7769372 was also positively associated with schizophrenia (permutated p = 0.046). Rs1883901 was found to be positively associated with bipolar disorder (allele: permutated p = 0.0085; genotype: permutated p = 0.0009; OR = 1.31 [95%CI = 1.12–1.52]). The A-G-G haplotype of rs1883901-rs10807187-rs9462343 was also positively associated with bipolar disorder with a global p value of 0.0391 after permutations. No individual SNP or haplotype was associated with major depressive disorder after permutations. Conclusion The MDGA1 gene may confer risk to schizophrenia and bipolar disorder in Chinese Han population.

Association analysis between BDNF gene polymorphism and the anxiety symptoms of depressive disorder in Chinese Han population

Oblectlve To explore the association of brain-derived neurotrophic factor(BDNF)gene polymorphism and the anxiety symptoms of depressive disorder in Chinese Han population.Methods A total of 458 depressive patients diagnosed by DSM-Ⅳ were admitted in the study.The severity of depression and anxiety were respectively assessed with 17-item Hamilton Depression Hating Scale(17-HAMD)and Hamilton Anxiety Scale (HAMA).Polymerase chain reaction(PCR)and DNA direct sequencing technique were used to detect the genetic polymorphism of the BDNF gene.The analyses of the quantitative trait were performed by UNPHASED(version 3.0).Results There were no significant differences between HAMA score and polymorphism of the BDNF gene rs6265(alleles:X2=1.947,P=0.163;genotypes:X2=2.184,P=0.336).An association between the polymorphism and the quantitative character of anxiety symptoms were observed in the allele(mental anxious factor:X2=4.908,P=0.027;anxious mood:X2=4.312,P=0.038),but not in the genotype.Other item score of HAMA was showed no association with polymorphism of the BDNF gene rs6265(P＞0.05).Conclusion The polymorphism in allele of BDNF gene may be associated with the anxiety symptoms of depressive patients.Polymorphism of the BDNF gene might constitute the appearance of the clinical manifestation-anxiety in depressive disorder.The result also suggests that the analysis of symptom phenotype may be more suitable for genetic study of depressive disorder. Key words: Depressive disorder; Anxiety; BDNF gene; Polymorphism

The association analysis of RELN and GRM8 genes with autistic spectrum disorder in chinese han population

The region on chromosome 7q stands out as the region of suggestive linkage to aetiology of autism with the greatest concordance in many independent genome-wide scans. RELN and GRM8, the two genes selected in this study, are located within this region. The protein products of both genes are considered to play a pivotal role in the development of the central nervous system. In addition, biochemical and neuroanatomical data indicated that RELN and GRM8 genes are likely involved in the pathogenesis of autistic disorder. Therefore, both RELN and GRM8 genes are considered to be not only the positional but also the functional candidate genes to autism for association research. In this study, we genotyped 12 single nucleotide polymorphisms (SNPs) located within the RELN and GRM8 genes in 213 children with autistic spectrum disorder (ASD) and 160 controls. A significant genetic association between SNP2 (located in intron 59 of RELN) and ASD was observed, and the log-additive model was accepted as the best inheritance model fitting this data (OR: 0.72, 95% CI: 0.54-0.97, P = 0.03). Haplotype-specific association analysis revealed that the result was consistent with the individual SNP study; the combination of SNP1/SNP2/SNP3/SNP4 which are in strong linkage disequilibrium (LD) (D' > 0.75) showed significant association with ASD (P = 0.027). Neither the single SNP nor the haplotype analysis showed significant association between ASD and the markers of GRM8 gene. Hence, our study suggested the possible involvement of RELN gene in the susceptibility to ASD. Future replications are warranted before definitive conclusion can be drawn.

Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population

Attention deficit hyperactivity disorder (ADHD) is a severe behavioral disorder in children known to have a substantial genetic component. Prior studies have implicated serotonin genes in the etiology of ADHD but have not examined tryptophan hydroxylase (TPH), which is a rate-limiting enzyme in serotonin biosynthesis. The current study examined the relationship between the A218C and A-6526G polymorphisms of the TPH gene and ADHD. Three hundred sixty-two unrelated ADHD probands and their biological parents were recruited to participate in this study. No biased transmission of any allele of the two polymorphisms was observed using TDT analysis. However, haplotype analyses found that the rare 218A/-6526G haplotype was significantly not transmitted to probands with ADHD (chi(2) = 4.4995, P = 0.034), regardless of subtype. Although this finding for ADHD in the Chinese Han population.

Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention-deficit hyperactivity disorder in Chinese Han population.

Previous studies have suggested that the serotonergic (5-HT) system might be involved in the development of Attention-deficit hyperactivity disorder (ADHD). ADHD is frequently characterized by aggressive and impulsive behavior, a major symptom associated with reduction in serotonergic function. The tryptophan hydroxylase (TPH) gene is a reasonable candidate for ADHD because it encodes the rate-limiting enzyme in the process of 5-HT biosynthesis. In this study, we examined the relationship between the A218C polymorphism in TPH gene and ADHD. Sixty-nine ADHD patients and their biological parents were investigated. The A218C polymorphism in intron 7 of TPH gene was detected by PCR-RFLP method. No allele or genotype concerned with this A218C polymorphism was found to be associated with ADHD when analyzed with the haplotype relative risk method. Therefore, our data indicate that the TPH gene A218C polymorphism may not be a susceptibility factor of ADHD in the Chinese Han population.