Cabanero Michael, Laje Gonzalo, Detera-Wadleigh Sevilla, McMahon Francis J
Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-3719, USA.
Pharmacogenet Genomics. 2009 Mar;19(3):235-8. doi: 10.1097/FPC.0b013e328320a3e2.
A recent study has reported a significant association of variants in phosphodiesterase (PDE) genes with antidepressant treatment outcome in a Mexican American sample. We set out to investigate these findings in a large sample of patients from the Sequenced Treatment Alternatives to Relieve Depression (STARD) study. STARD is a longitudinal study of antidepressant outcome in depressed outpatients. We genotyped three single nucleotide polymorphisms (SNPs) in PDE11A (rs1880916), PDE1A (rs1549870), and PDE9A (rs729861) for replication and we also report three additional SNPs in PDE11A (rs3770016, rs4893975, rs6433687) that had been genotyped for a previous study. Single marker analysis of remission within the Hispanic subsamples (n=268) revealed no significant evidence of association with markers in PDE11A, PDE9A, or PDE1A. Additional analyses of remission within the total STARD sample (n=1914) were also largely negative, as were analyses utilizing a narrower definition of remission. Haplotype analyses were carried out with the four PDE11A SNPs we genotyped; these also failed to show significant evidence of association in the STARD sample. In conclusion, we could not reproduce the reported association between PDE genes and antidepressant outcome in a sample of participants comparable to that reported previously. We conclude that PDE11A, PDE9A, and PDE1A are unlikely to play an important role in antidepressant outcome in this sample.
最近一项研究报告称,在一个墨西哥裔美国人样本中,磷酸二酯酶(PDE)基因变异与抗抑郁治疗结果之间存在显著关联。我们着手在来自缓解抑郁症序列治疗替代方案(STARD)研究的大量患者样本中调查这些发现。STARD是一项针对抑郁症门诊患者抗抑郁治疗结果的纵向研究。我们对PDE11A(rs1880916)、PDE1A(rs1549870)和PDE9A(rs729861)中的三个单核苷酸多态性(SNP)进行基因分型以进行重复验证,并且我们还报告了PDE11A中的另外三个SNP(rs3770016、rs4893975、rs6433687),这些SNP在之前的一项研究中已进行基因分型。对西班牙裔亚样本(n = 268)中的缓解情况进行单标记分析,未发现与PDE11A、PDE9A或PDE1A中的标记存在显著关联的证据。对整个STARD样本(n = 1914)中的缓解情况进行的其他分析在很大程度上也是阴性结果,使用更狭义的缓解定义进行的分析也是如此。我们对基因分型的四个PDE11A SNP进行了单倍型分析;这些分析在STARD样本中也未显示出显著的关联证据。总之,在与之前报告的样本相当的参与者样本中,我们无法重现所报告的PDE基因与抗抑郁治疗结果之间的关联。我们得出结论,在该样本中,PDE11A、PDE9A和PDE1A不太可能在抗抑郁治疗结果中发挥重要作用。