SSRI response in depression may be influenced by SNPs in HTR1B and HTR1A.
SSRI response in depression may be influenced by SNPs in HTR1B and HTR1A.
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DOI：
10.1097/ypg.0b013e32832a506e
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发表时间：
2009-12
影响因子：
0.9
通讯作者：
Burmeister M
中科院分区：
文献类型：
--
作者：
Villafuerte SM;Vallabhaneni K;Sliwerska E;McMahon FJ;Young EA;Burmeister M
5 -羟色胺1A （HTR1A）和1B （HTR1B）自身受体的脱敏被认为与SSRIs反应延迟有关。因此，这些基因表达的变异可能影响SSRI反应。在这里，我们在两个样本中测试了这一假设，这些样本来自于缓解抑郁症的测序治疗方案（STAR*D），并显示了几个基因变异单独和相互作用的证据。最初，我们分析了153名接受西酞普兰治疗的抑郁症患者的HTR1B基因和HTR1A基因的三个功能性snp。QIDS-C评分随时间的推移对遗传变异进行评估。HTR1A中- 1019g等位基因（rs6295）纯合子的受试者显示出更高的基线QIDS评分（p = 0.033），并且在12周时应答率显著降低（p = 0.005）。根据先前报道的体外表达水平估计HTR1B单倍型。高表达单倍型纯合子个体对西酞普兰的反应明显较慢（p = 0.034）。然后，我们在扩展的总体STAR*D样本中分析了更多的snp。虽然我们不能直接检测相同的功能snp，但我们发现HTR1A中rs1364043等位基因G的纯合子（p = 0.045）和HTR1B中rs6298等位基因C的纯合子随着时间的推移对西酞普兰的反应更好（p = 0.022）。HTR1B中的rs6298和HTR1A中的rs1364043之间的相互作用测试是显著的（总体p = 0.032）。我们的数据表明，在SSRI治疗期间，HTR1B或HTR1A转录活性的增强可能会损害自身受体的脱敏。
Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to SSRIs. Variations in gene expression in these genes may thus affect SSRI response. Here we test this hypothesis in two samples from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), and show evidence for involvement of several genetic variants alone and in interaction. Initially, three functional SNPs in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. QIDS-C scores were evaluated over time with respect to genetic variation. Subjects homozygous for the - 1019 G allele (rs6295) in HTR1A showed higher baseline QIDS scores (p = 0.033), and by 12 weeks had a significantly lower response rate (p = 0.005). HTR1B haplotypes were estimated according to previously reported in-vitro expression levels. Individuals who were homozygous for the high-expression haplotype showed significantly slower response to citalopram (p = 0.034). We then analyzed more SNPs in the extended overall STAR*D sample. Although we could not directly test the same functional SNPs, we found that homozygotes for the G allele at rs1364043 in HTR1A (p = 0.045) and the C allele of rs6298 in HTR1B showed better response to citalopram over time (p = 0.022). Test for interaction between rs6298 in HTR1B and rs1364043 in HTR1A was significant (overall p = 0.032) Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment.