Verma Ranjana, Cutler David J, Holmans Peter, Knowles James A, Crowe Raymond R, Scheftner William A, Weissman Myrna M, DePaulo J Raymond, Levinson Douglas F, Potash James B
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1079-82. doi: 10.1002/ajmg.b.30514.
Recent evidence suggests a potential role for the p11 gene in conferring risk to depressive disorders. p11 has been shown to influence serotonergic transmission, and its expression was found to be reduced in a mouse model of depression, as well as in post-mortem brain tissue from major depressive disorder (MDD) cases. In the present study, we tested for rare variants in p11 by resequencing promoter, exonic and flanking intronic regions in 176 MDD cases and 176 matched controls. We also assessed common variation by genotyping eight single nucleotide polymorphisms (SNPs), seven tag SNPs and one found through resequencing, in 641 cases and 650 controls. Resequencing revealed nine novel rare variants, including a missense mutation (Asp60Glu) observed in one case and one control, and four variants that occurred only in cases and not controls. The number of rare variants in cases did not exceed that expected by chance for the length of sequence analyzed, and also was not significantly greater than that observed in controls. Resequencing also identified two known SNPs, one (rs4845720) of which was significantly more frequent in cases than controls in the resequenced sample (3.1% vs. 0.9%, P = 0.03), though not in the larger sample (3% vs. 2%, P = 0.15). None of the tag SNPs showed any evidence of association. Our results do not support a major role for either common or rare p11 SNPs with MDD. Several limitations of the study are discussed.
最近的证据表明，p11基因在赋予抑郁症风险方面可能发挥作用。p11已被证明会影响血清素能传递，并且在抑郁症小鼠模型以及重度抑郁症（MDD）病例的死后脑组织中发现其表达降低。在本研究中，我们通过对176例MDD病例和176例匹配对照的启动子、外显子和侧翼内含子区域进行重测序，检测p11中的罕见变异。我们还通过对641例病例和650例对照进行8个单核苷酸多态性（SNP）、7个标签SNP和1个通过重测序发现的SNP的基因分型，评估常见变异。重测序揭示了9个新的罕见变异，包括在1例病例和1例对照中观察到的一个错义突变（Asp60Glu），以及4个仅在病例中出现而不在对照中出现的变异。病例中罕见变异的数量不超过分析序列长度的预期偶然数量，也没有显著大于在对照中观察到的数量。重测序还鉴定出两个已知的SNP，其中一个（rs4845720）在重测序样本中病例中的频率显著高于对照（3.1%对0.9%，P = 0.03），但在更大样本中并非如此（3%对2%，P = 0.15）。没有一个标签SNP显示出任何关联证据。我们的结果不支持常见或罕见的p11 SNP在MDD中起主要作用。讨论了该研究的几个局限性。
