Cheah Sern-Yih, Lawford Bruce R, Young Ross McD, Connor Jason P, Phillip Morris C, Voisey Joanne
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, QLD 4059, Australia.
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, QLD 4059, Australia Discipline of Psychiatry, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia.
Alcohol Alcohol. 2014 Sep-Oct;49(5):491-7. doi: 10.1093/alcalc/agu040. Epub 2014 Jul 3.
The functional BDNF single nucleotide polymorphism (SNP) rs6265 has been associated with many disorders including schizophrenia and alcohol dependence. However, studies have been inconsistent, reporting both positive and negative associations. Comorbid alcohol dependence has a high prevalence in schizophrenia so we investigated the role of rs6265 in alcohol dependence in Australian populations of schizophrenia and alcohol-dependent patients.
Two BDNF SNPs rs6265 and a nearby SNP rs7103411 were genotyped in a total of 848 individuals. These included a schizophrenia group (n = 157) and a second schizophrenia replication group (n = 235), an alcohol-dependent group (n = 231) that had no schizophrenia diagnosis and a group of healthy controls (n = 225).
Allelic association between rs7103411 and comorbid alcohol dependence was identified (P = 0.044) in the primary schizophrenia sample. In the replication study, we were able to detect allelic associations between both BDNF SNPs and comorbid alcohol dependence (rs6265, P = 0.006; rs7103411, P = 0.014). Moreover, we detected association between both SNPs and risk-taking behaviour after drinking (rs6265, P = 0.005; rs7103411, P = 0.009) and we detected strong association between both SNPs and alcohol dependence in males (rs6265, P = 0.009; rs7103411, P = 0.013) while females showed association with multiple behavioural measures reflecting repetitive alcohol consumption. Haplotype analysis revealed the rs6265-rs7103411 A/C haplotype is associated with comorbid alcohol dependence (P = 0.002). When these SNPs were tested in the non-schizophrenia alcohol-dependent group we were unable to detect association.
We conclude that these BDNF SNPs play a role in development of comorbid alcohol dependence in schizophrenia while our data do not indicate that they play a role in alcohol-dependent patients who do not have schizophrenia.
功能性脑源性神经营养因子单核苷酸多态性（SNP）rs6265与包括精神分裂症和酒精依赖在内的多种疾病相关。然而，研究结果并不一致，既有阳性关联报道，也有阴性关联报道。精神分裂症患者中酒精依赖共病的患病率较高，因此我们研究了rs6265在澳大利亚精神分裂症和酒精依赖患者群体中酒精依赖方面的作用。
对总共848名个体的两个脑源性神经营养因子SNP rs6265和附近的SNP rs7103411进行基因分型。这些个体包括一个精神分裂症组（n = 157）和第二个精神分裂症重复组（n = 235）、一个无精神分裂症诊断的酒精依赖组（n = 231）以及一组健康对照组（n = 225）。
在原发性精神分裂症样本中，确定了rs7103411与酒精依赖共病之间的等位基因关联（P = 0.044）。在重复研究中，我们能够检测到两个脑源性神经营养因子SNP与酒精依赖共病之间的等位基因关联（rs6265，P = 0.006；rs7103411，P = 0.014）。此外，我们检测到这两个SNP与饮酒后冒险行为之间的关联（rs6265，P = 0.005；rs7103411，P = 0.009），并且在男性中检测到这两个SNP与酒精依赖之间有很强的关联（rs6265，P = 0.009；rs7103411，P = 0.013），而女性则显示与反映反复饮酒的多种行为指标有关联。单倍型分析显示rs6265 - rs7103411 A/C单倍型与酒精依赖共病相关（P = 0.002）。当在无精神分裂症的酒精依赖组中对这些SNP进行检测时，我们未能检测到关联。
我们得出结论，这些脑源性神经营养因子SNP在精神分裂症患者酒精依赖共病的发生中起作用，而我们的数据并未表明它们在无精神分裂症的酒精依赖患者中起作用。
