CYP2C19-rs4986893 增加汉族人群发生重度抑郁症和双相情感障碍的风险，而 ABCB1-rs1045642 则作为一个保护因素。
CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor.
机构信息
Clinical Laboratory, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
Affective Disorder Department, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
出版信息
BMC Psychiatry. 2023 Jan 25;23(1):69. doi: 10.1186/s12888-022-04514-w.
BACKGROUND
Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population.
METHODS
Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software.
RESULTS
Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001).
CONCLUSION
Our data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor.
背景
遗传风险可能以不同的方式使个体易患主要心境障碍。本研究旨在调查先前报道的用于重度抑郁症（MDD）和双相障碍（BPD）候选基因的基因多态性在汉族人群中的情况。
方法
采用基质辅助激光解吸电离飞行时间质谱法（MALDI-TOF MS）对 439 例 MDD 患者、600 例 BPD 患者和 464 例健康对照者的 13 个候选基因的 20 个位点进行检测。使用 PLINK 软件分析等位基因、哈迪-温伯格平衡和遗传关联的基因型分布。使用 Haploview 软件进行连锁不平衡和单倍型分析。
结果
在分析的 20 个位点中，CYP2C19-rs4986893、ABCB1-rs1045642 和 SCN2A-rs17183814 经 Bonferroni 校正后具有统计学意义；其统计效能均>55%。MDD 组（0.0547）和 BPD 组（0.0533）的 CYP2C19-rs4986893 等位基因的次要等位基因频率（MAF）高于对照组（0.0259，P<0.05），导致 MDD（2.178）和 BPD（2.122）的比值比（OR）分别为 2.178 和 2.122。相比之下，MDD（0.3599，OR=0.726）和 BPD（0.3700，OR=0.758）组中 ABCB1-rs1045642 的 MAF 均低于对照组（0.4364，P<0.05）。SCN2A-rs17183814 的 MAF 在 MDD 组中高于对照组（0.1743 比 0.1207，OR=1.538，P<0.05）。此外，由 CYP2C19-rs4986893 和 -rs4244285 组成的 G-A 单倍型与 BPD 相关（OR=1.361，P<0.01），A-G 单倍型增加了 MDD（OR=2.306，P<0.01）和 BPD（OR=2.332，P<0.001）的发病风险。CYP2C19 中间代谢型和弱代谢型（IM&PM）状态与 MDD（OR=1.547，P<0.01）和 BPD（OR=1.808，P<0.001）的发病风险升高有关。
结论
我们的数据表明，由 CYP2C19 等位基因组成的单倍型引起的 CYP2C19 代谢受损可能导致 MDD 和 BPD 的发病风险增加，而 ABCB1-rs1045642 的 T 等位基因则是一种保护因素。
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