Xie Xiaohu, Zhuang Dingding, Gu Jun, Wu Tingting, Shen Wenwen, Li Longhui, Liu Yue, Xu Wenjin, Hong Qingxiao, Xu Zemin, Chen Weisheng, Zhou Wenhua, Liu Huifen
Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.
Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.
Neurosci Lett. 2023 Mar 13;800:137137. doi: 10.1016/j.neulet.2023.137137. Epub 2023 Feb 18.
Evidence reveals that γ-aminobutyric acid (GABA) receptors are involved in the development of methamphetamine (METH) dependence. The GABA receptor delta subunit gene (GABRD) might be a good candidate gene for METH dependence. In a case-control study, we investigated the association between the single nucleotide polymorphisms (SNPs) in GABRD and METH dependence in a Chinese Han population.
A total of 300 METH dependent patients and 300 age and sex matched normal control subjects were recruited. Four SNPs (rs13303344, rs4481796, rs2376805, and rs2229110) in GABRD were determined with the TaqMan genotyping assay. The association of the SNPs with METH dependence was assessed.
Only the allele frequency of rs2376805 significantly differed between the patients and controls (P = 0.030). The G allele frequency of rs2376805 was higher in the METH dependent group than in the controls (odds ratio = 1.332, 95 % CI: 1.028-1.724). This association was found in females but not in males. In females, the frequencies of genotype and allele at rs2376805 significantly differed between the patients and controls (P = 0.025, 0.022, respectively); the rs2376805 G allele may also be a risk factor for METH dependence (odds ratio = 1.548, 95 % CI: 1.063-2.257). The haplotype ACGT frequency significantly differed between the patients and controls in total subjects (P = 0.008, odds ratio = 1.815, 95 % CI: 1.183-2.782), as well as in females (P = 0.005, odds ratio = 2.702, 95 % CI: 1.313-5.562). In females only, the METH craving score was significantly lower in patients harboring the G allele at rs2376805 than in those harboring the homozygous AA genotype (P = 0.044).
The preliminary results indicate that GABRD rs2376805 is associated with METH dependence, especially in females.
有证据表明γ-氨基丁酸（GABA）受体参与甲基苯丙胺（METH）依赖的形成。GABA受体δ亚基基因（GABRD）可能是METH依赖的一个良好候选基因。在一项病例对照研究中，我们调查了中国汉族人群中GABRD单核苷酸多态性（SNP）与METH依赖之间的关联。
共招募了300例METH依赖患者和300例年龄及性别匹配的正常对照者。采用TaqMan基因分型检测法确定GABRD中的4个SNP（rs13303344、rs4481796、rs2376805和rs2229110）。评估这些SNP与METH依赖的关联。
仅rs2376805的等位基因频率在患者和对照者之间存在显著差异（P = 0.030）。rs2376805的G等位基因频率在METH依赖组中高于对照组（优势比 = 1.332，95%可信区间：1.028 - 1.724）。这种关联在女性中存在，而在男性中未发现。在女性中，rs2376805的基因型和等位基因频率在患者和对照者之间存在显著差异（分别为P = 0.025、0.022）；rs2376805的G等位基因也可能是METH依赖的一个危险因素（优势比 = 1.548，95%可信区间：1.063 - 2.257）。单倍型ACGT频率在总体研究对象中患者和对照者之间存在显著差异（P = 0.008，优势比 = 1.815，95%可信区间：1.183 - 2.782），在女性中也是如此（P = 0.005，优势比 = 2.702，95%可信区间：1.313 - 5.562）。仅在女性中，rs2376805携带G等位基因的患者的METH渴求评分显著低于携带纯合AA基因型的患者（P = 0.044）。
初步结果表明GABRD rs2376805与METH依赖相关，尤其是在女性中。
