Gene-Based Association Analysis Suggests Association of HTR2A With Antidepressant Treatment Response in Depressed Patients

Chung-Feng Kao; Po-Hsiu Kuo; Younger W-Y Yu; Albert C Yang; Eugene Lin; Yu-Li Liu; Shih-Jen Tsai

doi:10.3389/fphar.2020.559601

Gene-Based Association Analysis Suggests Association of HTR2A With Antidepressant Treatment Response in Depressed Patients

Front Pharmacol. 2020 Dec 3:11:559601. doi: 10.3389/fphar.2020.559601. eCollection 2020.

Authors

Chung-Feng Kao^{1

2}, Po-Hsiu Kuo^{3

4}, Younger W-Y Yu⁵, Albert C Yang^{6

7

8}, Eugene Lin^{9

10

11}, Yu-Li Liu¹², Shih-Jen Tsai^{13

14}

Affiliations

¹ Department of Agronomy, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung, Taiwan.
² Advanced Plant Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
³ Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
⁴ Department of Public Health, National Taiwan University, Taipei, Taiwan.
⁵ Yu's Psychiatric Clinic, Kaohsiung, Taiwan.
⁶ Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
⁷ Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
⁸ Brain Medicine Center, Taoyuan Psychiatric Center, Taoyuan City, Taiwan.
⁹ Department of Biostatistics, University of Washington, Seattle, WA, United States.
¹⁰ Department of Electrical & Computer Engineering, University of Washington, Seattle, WA, United States.
¹¹ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
¹² Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan Town, Taiwan.
¹³ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁴ Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan.

Abstract

The serotonin [5-hydroxytryptamine (5-HT)] system has been implicated in the pathogenesis of major depressive disorder (MDD). Among the 5-HT receptor subtypes, 5-HT2 is one of the major pharmacological therapeutic targets for MDD. There have been inconsistent findings in previous pharmacogenetic studies investigating the antidepressant therapeutic response using one or several 5-HT2A (HTR2A) genetic polymorphisms. By using gene-based association analysis, we hope to identify genetic variants of HTR2A which are related to MDD susceptibility and its antidepressant therapeutic response. 288 HTR2A single nucleotide polymorphisms in MDD susceptibility have been investigated through a case-control (455 MDD patients and 2, 998 healthy controls) study, as well as in antidepressant efficacy (n = 455) in our current research. The 21-item Hamilton Rating Scale for Depression was used to evaluate measures of antidepressant therapeutic efficacy. From two MDD groups in the antidepressant therapeutic response, by using gene-based analyses, we have identified 14 polymorphisms as suggestive markers for therapeutic response (13 for remission and 1 for response) in both meta- and mega-analyses. All of these HTR2A reported polymorphisms did not reach statistical significance in the case-control association study. This current investigation supported the link between HTR2A variants and antidepressant therapeutic response in MDD but not with MDD susceptibility.

Keywords: 5-hydroxytryptamine receptor 2A; antidepressant; gene-based analysis; major depressive disorders; single nucleotide polymorphism.