Yanfei Cao

ABCB6, ABCB1 and ABCG1 genetic polymorphisms and antidepressant response of SSRIs in Chinese depressive patients

AIM Major depressive disorder is a common psychiatric disorder with worldwide prevalence. The most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs). ATP-binding cassette proteins are responsible for the membrane transport of various molecules including antidepressive drugs. We investigated whether SNPs in ABCB6, ABCB1 and ABCG1 were associated with the treatment response of SSRIs. MATERIALS & METHODS A pharmacogenetic study genotyping nine SNPs was conducted in 290 major depressive disorder patients in the Chinese Han population. Allele and genotype frequencies were compared between responders and nonresponders. RESULTS The allele frequencies of rs28401781 and rs4148739 in ABCB1 showed significant difference between responders and nonresponders before correction (p = 0.0297 and p = 0.0359, respectively). No significant associations were detected for the ABCB6 or ABCG1 gene. CONCLUSION Our results suggest that ABCB1 polymorphisms might be associated with SSRIs treatment response in the Chinese Han population.

No association of SLC6A3 and SLC6A4 gene polymorphisms with schizophrenia in the Han Chinese population

The SLC6A3 and SLC6A4 genes are members of a class of neurotransmitter transporters for the release, re-uptake and recycling of neurotransmitters in synapses. SLC6A3 and SLC6A4 encode a dopamine transporter and serotonin transporter, respectively. Abnormal expression and genetic polymorphism of SLC6A3 and SLC6A4 genes may increase the risk of developing mental illness, such as schizophrenia, bipolar disorder, ADHD, and aggressive behavior in Alzheimer disease, etc. Nevertheless, association between SLC6A3, SLC6A4 genes polymorphism and schizophrenia patients have not been well studied in Han Chinese people. In this study, we examined whether single nucleotide polymorphisms (SNPs) in SLC6A3, SLC6A4 were associated with schizophrenia in Han Chinese people (893 schizophrenia patients and 611 healthy controls). No significant difference in allelic or genotypic frequency was found between schizophrenia patients and healthy controls. No positive linkage disequilibrium (LD) was detected either. No haplotypic distributions were positive. Accordingly, our study suggests that the 10 SNPs within both genes we examined do not play a major role in schizophrenia in the Han Chinese population.

Allele-specific expression of mutated in colorectal cancer ( MCC ) gene and alternative susceptibility to colorectal cancer in schizophrenia

Evidence has indicated that the incidence of colorectal cancer (CRC) among schizophrenia is lower than normal. To explore this potential protective effect, we employed an innovative strategy combining association study with allele-specific expression (ASE) analysis in MCC gene. We first genotyped four polymorphisms within MCC in 312 CRC patients, 270 schizophrenia patients and 270 controls. Using the MassArray technique, we performed ASE measurements in a second sample series consisting of 50 sporadic CRC patients, 50 schizophrenia patients and 52 controls. Rs2227947 showed significant differences between schizophrenia cases and controls, and haplotype analysis reported some significant discrepancies among these three subject groups. ASE values of rs2227948 and rs2227947 presented consistently differences between CRC (or schizophrenia) patients and controls. Of the three groups, highest frequencies of ASE in MCC were concordantly found in CRC group, whereas lowest frequencies of ASE were observed in schizophrenia group. Similar trends were confirmed in both haplotype frequencies and ASE frequencies (i.e. CRC > control > schizophrenia). We provide a first indication that MCC might confer alterative genetic susceptibility to CRC in individuals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression.

Association study of 5-HT1A, 5-HT2A polymorphisms with schizophrenia and major depressive disorder in the Han Chinese population

Schizophrenia (SZ) and major depressive disorder (MDD) are two common severe mental disorders that have arisen to public awareness in recent years. Serotonin (5-HT) receptors have been implicated in the pathophysiology of psychiatric disorders especially in MDD and SZ. The aim of this study is to explore whether the variants in the 5-HT1A and 5-HT2A gene are susceptible to SZ or MDD in the Chinese Han population. Five SNPs (Single Nucleotide Polymorphisms) (rs1364043, rs10042486, rs6313, rs6311, rs17289304) in these genes were genotyped from 752 SZ patients, 568 MDD patients, and 846 normal controls of Chinese Han origin. The results showed that the 5-HT1A rs10042486 was significantly associated with SZ (Pallele=0.0369, Pgenotype=0.0098). Moreover, the haplotype (C-T) composed of rs10042486 and rs1364043 showed significant difference between SZ cases and healthy controls (P=0.0302) while another haplotype (T-G) was significant for MDD (P=0.0247). Our study is the first to suggest a positive association of the 5-HT1A gene with SZ in the Han Chinese population.

No association between SLC6A2, SLC6A3, DRD2 polymorphisms and schizophrenia in the Han Chinese population

This study was intended to ascertain whether SNPs in dopaminergic and serotoninergic pathway genes SLC6A2, SLC6A3 and DRD2 are associated with schizophrenia in Han Chinese people. We conducted a case-control study by genotyping 7 SNPs of the three genes in 1034 schizophrenia patients and 1034 controls. No significant difference in the allelic or genotypic frequency was detected between cases and controls despite one positive haplotype (rs1362621-rs2242446-rs5564). Stratified analysis of gender and gene-gene interaction analysis showed no positive results. In summary, our study denies the major role of these SNPs within the three genes for schizophrenia in Han Chinese.

A study of single nucleotide polymorphisms of GRIN2B in schizophrenia from Chinese Han population

Schizophrenia is a severe and complex mental disorder with high heritability. There is evidence that mutations in the gene of Nmethyl-d-aspartate-type glutamate receptors (NMDAR) are associated with schizophrenia. GRIN2B encodes a subunit of NMDARs, and has been identified as a candidate gene for many psychiatric disorders, especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRIN2B were associated with schizophrenia. Four SNPs (rs890, rs1806191, rs219872, rs172677) were genotyped in 752 schizophrenic patients and 846 healthy controls of the Chinese Han population. Our results indicate differences in allele and genotype frequencies of rs890 between case and control. These results were assessed by adapting different genetic models (codominant, dominant, recessive, overdominant, log-additive models). After controlling for confounding factors including sex and age, rs890 remained associated with schizophrenia. In addition, rs890 and rs1806191 were found to form a haplotype associated with schizophrenia. In summary, our results indicate that the GRIN2B SNP rs890 might be associated with schizophrenia in the Chinese Han population.

Association study of TPH2 polymorphisms and bipolar disorder in the Han Chinese population.

OBJECTIVE Bipolar disorder (BPD) is a serious and common mental disorder with high heritability. The serotonergic system is known to be implicated in the etiology of the disorder. Tryptophan hydroxylase isoform-2 (TPH2), which controls the synthesis of serotonin in the brain, has been suggested as a candidate gene for BDP. The aim of this study was to examine the association between the polymorphisms in TPH2 and BPD. METHODS We conducted a case-control study by genotyping six SNPs (rs10784941, rs1386494, rs2171363, rs4760816, rs1386486, and rs1872824) in 506 bipolar patients and 507 controls of Chinese Han origin. RESULTS rs10784941 was not in the Hardy-Weinberg equilibrium and therefore excluded from further analysis. rs1386486 and rs1872824 showed statistically significant differences between cases and controls in genotype frequencies (rs1386486: p=0.043351; rs1872824: p=0.016563), but no association in allele frequencies. Strong LD was found among rs1386494, rs2171363 and rs4760816, but no positive association with BPD was found for haplotypes. CONCLUSION Our results indicate that in the Han Chinese population TPH2 may be a potential susceptibility gene for bipolar disorder. Further studies are needed to validate this association.

Association study between ABCB1, ABCB6 and ABCG1 polymorphisms and major depressive disorder in the Chinese Han population

Please cite this article as: Gaini Ma , Xiaoye Huang , Yan Bi , Decheng Ren , Fei Xu , Qianqian Sun , Rui Zhang , Jiaxin Hu , Weibo Niu , Zhenming Guo , Ruixue Yuan , Fan Yuan , Xi Wu , Yanfei Cao , Fengping Yang , Lu Wang , Weidong Li , Tao Yu , Lin He , Jie Liu , Guang He , Xingwang Li , Association study between ABCB1, ABCB6 and ABCG1 polymorphisms and major depressive disorder in the Chinese Han population , Psychiatry Research (2018), doi: 10.1016/j.psychres.2018.05.045

No association of GRIK4 polymorphisms with schizophrenia in the Chinese Han population

Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Institute of Mental Health, Shanghai Jiao Tong University and Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China Correspondence to Xingwang Li, PhD, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People’s Republic of China Tel/fax: + 86 21 6282 2491; e-mail: xwli@sjtu.edu.cn

Common variants in GRIK4 and major depressive disorder: An association study in the Chinese Han population

Major depressive disorder (MDD) is a common and complex mental disorder. Recent studies found that genetic variants located in GRIK4, which encoded glutamate ionotropic receptor kainate type subunit 4, was associated with the MDD. In this study, we intended to investigate whether GRIK4 gene was associated with MDD. So five single nucleotide polymorphisms (SNPs) were selected and genotyped (rs79526501, rs11218016, rs4582985, rs6589847, rs56275759) in 568 MDD patients and 846 healthy controls from Chinese Han population. The results showed that rs56275759 demonstrated statistically significant differences between MDD patients and control subjects both in allelic frequencies (p value=0.011) and genotypic frequencies (p value=0.029). Rs4582985 was excluded from the further analysis for its deviation from the Hardy-Weinberg equilibrium. Strong linkage disequilibrium (LD) was found among rs11218016, rs6589847 and rs56275759, and this block was significantly associated with MDD. In summary, our results firstly indicated that rs56275759 of GRIK4 gene might be associated with MDD in Chinese Han population.