International Journal of Biomedicine. 2018;8(3):186-191.
Originally published September 15, 2018
The purpose of our research was to study the association of the HTR2A T102C (rs6313) SNP with anthropometric and biochemical markers in patients treated with typical and atypical antipsychotics in monotherapy mode.
Materials and methods: One hundred and seventeen white inpatients (95 men and 22 women) with F2 disorders (ICD-10, 1995) were enrolled in the study. All patients were divided into two groups by the antipsychotic class with which they were treated (Group 1 included 40 patients treated with typical antipsychotics; Group 2 included 77 patients treated with atypical antipsychotics) and two subgroups by weight change criteria during the study (Subgroup 1 included patients with weight change >6%; Subgroup 2 included patients with weight change <6%). The following examinations were performed: physical examination, anthropometric measurements (BMI. WC, TC), clinical examination, blood test (ALT, AST, FPG, VLDL-C, LDL-C, HDL-C, total cholesterol, triglycerides, total protein, albumin, creatinine, uric acid, carbamide), and genotyping for the HTR2A T102C (rs6313) SNP.
Results: There were no statistically significant differences in the distribution of genotypes of the HTR2A T102C (rs6313) SNP between Group 1 and Group 2 (P>0.05). Kruskal-Wallis one-way analysis of variance between subgroups showed statistically significant differences between carbamide levels in the second visit in Group 2 (P=0.02). A Dunn post hoc test with Bonferroni adjustment showed statistically significant differences between TT and CT genotypes of the HTR2A T102C SNP: carbamide level was greater in TT carriers (P=0.02). The strength of associations and risks between alleles of the HTR2A T102C SNP and antipsychotic-induced weight change were as follows: ORC=0.49; CIC [0.25; 0.95]; RRC=0.58 CIC [0.35; 0.97]; ORT=2.03; CIT [1.05; 3.94]; RRT=1.7 CIT [1.02; 2.81].
Conclusion: Our results of the pilot pharmacogenetic studies show an association of the T allele carriage of the HTR2A T102C SNP with risk of antipsychotic-induced weight gain. The continuation of this study and an increase in the sample size will allow establishing valid pharmacogenetic markers for the risk of antipsychotic-induced weight gain.
- Zhang JP, Malhotra AK. Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction. Expert Opin Drug Metab Toxicol. 2011;7(1):9-37. doi: 10.1517/17425255.2011.532787. PubMed
- Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, et al. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry. 2006;63(10):1079-87. PubMed
- Nasyrova RF, Ivanov MV, Neznanov NG. Introduction to psychopharmacogenetics. St. Petersburg; 2015. [In Russian].
- Kuroki T, Nagao N, Nakahara T. Neuropharmacology of second-generation antipsychotic drugs: a validity of the serotonin-dopamine hypothesis. Prog Brain Res. 2008;172:199–212. doi: 10.1016/S0079-6123(08)00910-2. PubMed
- Horacek J, Bubenikova-Valesova V, Kopecek M, Palenicek T, Dockery C, Mohr P, Höschl C. Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs. 2006;20(5):389–409. PubMed
- Nasyrova RF, Tolmachev MY, Sychev DA, Yakhin KK, Neznanov NG. [Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect]. Bulletin of Siberian Medicine. 2017;16(4):30-41. [Article in Russian]. doi: 10.20538/1682-0363-2017-4-30-41
- Lencz T, Robinson DG, Napolitano B, Sevy S, Kane JM, Goldman D, Malhotra AK. DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenet Genomics. 2010;20(9):569–72. doi: 10.1097/fpc.0b013e32833ca24b. PubMed
- Maslovskiĭ SIu, Kozlovskiĭ VL. [Antipsychotic-induced weight gain: the possibilities of pharmacological correction]. Zh Nevrol Psikhiatr Iim S S Korsakova. 2008;108:8:81-6. [Article in Russian]. PubMed
- Dickerson FB, Brown CH, Kreyenbuhl, JA, Fang L, Goldberg RW, Wohlheiter K, Dixon LB. Obesity among individuals with serious mental illness. Acta Psychiatr Scand. 2006;113(4):306–13. PubMed
- Haslam DW, James WP. Obesity. Lancet. 2005;366(9492):1197–209. PubMed
- Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment – pharmacological mechanisms. Pharmacol Ther. 2010;125(1):169–79. doi: 10.1016/j.pharmthera.2009.10.010. PubMed
- Barnes NM, SharpT. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38(8):1083–152. PubMed
- Polesskaya OO, Sokolov BP. Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J Neurosci Res. 2002;67:812–22. PubMed
- Myers RL, Airey DC, Manier DH, Shelton RC, Sanders-Bush E. Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression. Biol Psychiatry. 2007;61(2):167-73. PubMed
- Turecki G, Brière R, Dewar K, Antonetti T, Lesage AD, Séguin M, et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry. 1999;156(9): 1456–8. PubMed
- Aghajanian GK, Marek GJ. Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology.1997;36(4-5):589–99. PubMed
- Lane HY, Liu YC, Huang CL, Chang YC, Wu PL, Lu CT, Chang WH. Risperidone-related weight gain: genetic and nongenetic predictors. J Clin Psychopharmacol. 2006;26(2):128–34. PubMed
- Prado-Lima PS, Cruz IB., Schwanke CH, Netto CA, Licinio J. Human food preferences are associated with a 5-HT(2A) serotonergic receptor polymorphism. Mol Psychiatry. 2006;11(10):889–91. PubMed
- Parsons MJ, D’Souza UM, Arranz MJ, Kerwin RW, Makoff AJ. The -1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity. Biol Psychiatry. 2004;56(6):406–10. PubMed
- Brecher M, Leong RW, Stening G, Osterling-Koskinen L, Jones AM. Quetiapine and long-term weight change: a comprehensive data review of patients with schizophrenia. J Clin Psychiatry. 2007;68(4):597–603. PubMed
Received June 14, 2018.
Accepted July 3, 2018.
©2018 International Medical Research and Development Corporation.