A 35.8 kilobases haplotype spanning ANKK1 and DRD2 is associated with heroin dependence in Han Chinese males
A 35.8 kilobases haplotype spanning ANKK1 and DRD2 is associated with heroin dependence in Han Chinese males
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跨越ANKK1和DRD2的35.8kb单倍型与中国汉族男性的海洛因依赖相关
DOI：
10.1016/j.brainres.2018.03.017
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发表时间：
2018-06-01
期刊：
影响因子：
2.9
通讯作者：
Zhu，Yongsheng
中科院分区：
文献类型：
--
作者：
Zhang，Jianbo;Yan，Peng;Zhu，Yongsheng
Ankyrin重复序列和包含1个激活域(ANKK1)和多巴胺受体D2(DRD2)基因的多态一直被认为与海洛因依赖的易感性有关。尽管ANKK1和DRD2相邻，但很少有研究阐明ANKK1和DRD2之间的潜在相互作用在海洛因依赖中的作用。在本研究中，我们系统地分析了这两个基因的39个单核苷酸多态(SNPs)与593名中国人海洛因依赖的关系。根据我们的结果，4个未报道的基因座的多态性与海洛因依赖有关，其中ANKK1的rs11214598经多次检测仍有显著意义。我们还对被广泛研究的变异rs1800497与海洛因依赖之间的关联进行了荟萃分析，作为代表性的例子，并获得了与我们的结果一致的结果。值得注意的是，跨越ANKK1和DRD2的35.8千碱基(Kb)单倍型被发现是海洛因依赖的强大保护因素。基因-基因互作分析表明，ANKK1中的rs11214598和DRD2中的rs1800497以及DRD2中的rs2245805和rs1079597之间存在互作。我们的研究强调了在遗传关联研究中考虑跨越相邻基因的单倍型以及近端变异或基因的合作和相互作用的重要性。
Ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine receptor D2 (DRD2) gene polymorphisms have long been considered to contribute to susceptibility to heroin dependence. Despite their adjacent locations, few studies have elucidated the role of the potential interaction betweenANKK1andDRD2in heroin dependence. In the present study, we performed a systematic analysis of the association between 39 single nucleotide polymorphisms (SNPs) in these two genes and heroin dependence in 593 Chinese subjects. According to our results, polymorphisms of four unreported loci were associated with heroin dependence, among which rs11214598 ofANKK1were still significant after multiple testing. We also conducted a meta-analysis of the association between a widely studied variant, rs1800497, and heroin dependence as a representative example and obtained a consistent outcome with our results. Notably, a 35.8 kilobases (kb) haplotype spanningANKK1andDRD2was found to be a strong protective factor for heroin dependence. Gene-gene interaction analysis suggested that interactions exist within theANKK1-DRD2haplotype block between rs11214598 and rs1800497 inANKK1and rs2245805 and rs1079597 inDRD2. Our study highlights the importance of considering haplotypes spanning adjacent genes and the cooperation and interaction of proximal variants or genes in genetic association studies.