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Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels.
Human Brain Mapping ( IF 3.5 ) Pub Date : 2020-07-22 , DOI: 10.1002/hbm.25138 Marie Spies 1, 2 , Arafat Nasser 1 , Brice Ozenne 1, 3 , Peter S Jensen 1 , Gitte M Knudsen 1 , Patrick M Fisher 1
Human Brain Mapping ( IF 3.5 ) Pub Date : 2020-07-22 , DOI: 10.1002/hbm.25138 Marie Spies 1, 2 , Arafat Nasser 1 , Brice Ozenne 1, 3 , Peter S Jensen 1 , Gitte M Knudsen 1 , Patrick M Fisher 1
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The serotonin 2A receptor (5‐HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18F]altanserin and [11C]Cimbi‐36 positron emission tomography (PET) allow for high‐resolution imaging of 5‐HT2AR in the living human brain. Cerebral 5‐HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5‐HT2AR or other serotonin (5‐HT) proteins, their effect on human in vivo brain 5‐HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5‐HTTLPR predict neocortex in vivo 5‐HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18F]altanserin or [11C]Cimbi‐36 PET. Although we observed genotype group differences in 5‐HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5‐HT2AR binding in what is the largest human in vivo 5‐HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5‐HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5‐HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5‐HT2AR binding.
中文翻译：
常见的 HTR2A 变体和 5-HTTLPR 与人体内 5-羟色胺 2A 受体水平无关。
血清素 2A 受体 (5-HT2AR) 与各种精神疾病的病理生理学和治疗有关。[ 18 F]altanserin 和[ 11 C]Cimbi-36 正电子发射断层扫描 (PET) 允许在活人脑中对 5-HT2AR 进行高分辨率成像。尽管对特定变异的影响知之甚少，但大脑 5-HT2AR 的结合是由遗传决定的。候选基因研究表明HTR2A包括 rs6311/rs6313、rs6314 和 rs7997012 在内的单核苷酸多态性可能会影响精神疾病的风险并介导治疗反应。尽管已知会影响 5-HT2AR 或其他血清素 (5-HT) 蛋白的体外表达，但它们对人体内脑 5-HT2AR 结合的影响尚未得到充分研究。因此，我们评估了这些变体和普遍研究的 5-HTTLPR 预测健康成年人体内新皮质 5-HT2AR 结合的程度。我们对 197 名用 [ 18 F] altanserin 或 [ 11C]Cimbi-36 PET。尽管我们观察到 5-HT2AR 结合的基因型组差异高达约 10%，但在迄今为止最大的人类体内 5-HT2AR 成像遗传学研究中，没有任何遗传变异在统计学上显着预测 5-HT2AR 结合。因此，体外和验尸结果表明对 5-HT2AR 表达的影响并未延续到体内环境中。在任何程度上，这些变异可能会影响临床风险，我们的研究结果不支持 5-HT2AR 结合介导这种影响。我们的观察表明，这些个体变异对人体内 5-HT2AR 结合的遗传负荷没有显着贡献。
更新日期：2020-07-22
中文翻译：
常见的 HTR2A 变体和 5-HTTLPR 与人体内 5-羟色胺 2A 受体水平无关。
血清素 2A 受体 (5-HT2AR) 与各种精神疾病的病理生理学和治疗有关。[ 18 F]altanserin 和[ 11 C]Cimbi-36 正电子发射断层扫描 (PET) 允许在活人脑中对 5-HT2AR 进行高分辨率成像。尽管对特定变异的影响知之甚少，但大脑 5-HT2AR 的结合是由遗传决定的。候选基因研究表明HTR2A包括 rs6311/rs6313、rs6314 和 rs7997012 在内的单核苷酸多态性可能会影响精神疾病的风险并介导治疗反应。尽管已知会影响 5-HT2AR 或其他血清素 (5-HT) 蛋白的体外表达，但它们对人体内脑 5-HT2AR 结合的影响尚未得到充分研究。因此，我们评估了这些变体和普遍研究的 5-HTTLPR 预测健康成年人体内新皮质 5-HT2AR 结合的程度。我们对 197 名用 [ 18 F] altanserin 或 [ 11C]Cimbi-36 PET。尽管我们观察到 5-HT2AR 结合的基因型组差异高达约 10%，但在迄今为止最大的人类体内 5-HT2AR 成像遗传学研究中，没有任何遗传变异在统计学上显着预测 5-HT2AR 结合。因此，体外和验尸结果表明对 5-HT2AR 表达的影响并未延续到体内环境中。在任何程度上，这些变异可能会影响临床风险，我们的研究结果不支持 5-HT2AR 结合介导这种影响。我们的观察表明，这些个体变异对人体内 5-HT2AR 结合的遗传负荷没有显着贡献。
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