GABRB2 Haplotype Association with Heroin Dependence in Chinese Population

PLoS One

Zhonghua Su¹  Jinsong Tang¹  Siyu Liu²  Yung Su Kim²  Yanhui Liao²  Wai-Kin Mat²  Shui-Ying Tsang²  Frank Pun²  Taobo Hu²  Xiaogang Chen³  Hong Xue³  Mei Yang³  Wei Hao³  Xianfei Jiang⁴  Siu-Kin Ng⁴ 

[1] Center for Statistical Science, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China;Division of Life Science and Applied Genomics Center, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China;Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, China;The Second Affiliated Hospital of Jining Medical College, Jining, Shandong, China

关键词: Haplotypes;    Heroin;    Schizophrenia;    Variant genotypes;    Polymerase chain reaction;    Genetic predisposition;    Han Chinese people;    Molecular genetics;   

DOI  :  10.1371/journal.pone.0142049

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Substance dependence is a frequently observed comorbid disorder in schizophrenia, but little is known about genetic factors possibly shared between the two psychotic disorders. GABRB2, a schizophrenia candidate gene coding for GABAA receptor β2 subunit, is examined for possible association with heroin dependence in Han Chinese population. Four single nucleotide polymorphisms (SNPs) in GABRB2, namely rs6556547 (S1), rs1816071 (S3), rs18016072 (S5), and rs187269 (S29), previously associated with schizophrenia, were examined for their association with heroin dependence. Two additional SNPs, rs10051667 (S31) and rs967771 (S32), previously associated with alcohol dependence and bipolar disorder respectively, were also analyzed. The six SNPs were genotyped by direct sequencing of PCR amplicons of target regions for 564 heroin dependent individuals and 498 controls of Han Chinese origin. Interestingly, it was found that recombination between the haplotypes of all-derived-allele (H1; OR = 1.00) and all-ancestral-allele (H2; OR = 0.74) at S5-S29 junction generated two recombinants H3 (OR = 8.51) and H4 (OR = 5.58), both conferring high susceptibility to heroin dependence. Additional recombination between H2 and H3 haplotypes at S1-S3 junction resulted in a risk-conferring haplotype H5 (OR = 1.94x109). In contrast, recombination between H1 and H2 haplotypes at S3-S5 junction rescued the risk-conferring effect of recombination at S5-S29 junction, giving rise to the protective haplotype H6 (OR = 0.68). Risk-conferring effects of S1-S3 and S5-S29 crossovers and protective effects of S3-S5 crossover were seen in both pure heroin dependent and multiple substance dependence subgroups. In conclusion, significant association was found with haplotypes of the S1-S29 segment in GABRB2 for heroin dependence in Han Chinese population. Local recombination was an important determining factor for switching haplotypes between risk-conferring and protective statuses. The present study provide evidence for the schizophrenia candidate gene GABRB2 to play a role in heroin dependence, but replication of these findings is required.

【 授权许可】

CC BY