Genetic polymorphisms of HTR2C, LEP and LEPR on metabolic syndromes in patients treated with atypical antipsychotic drugs

Puangpetch, Apichaya; Unaharassamee, Weerapon; Jiratjintana, Napa; Koomdee, Napatrupron; Sukasem, Chonlaphat

doi:10.1111/jphp.12892

Cited by 16 publications

(14 citation statements)

References 32 publications

(37 reference statements)

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“…Gender based differences in the effects of the long-term use of antipsychotics were noticed in this study; specifically, male patients experienced a significant development of four metabolic syndrome criteria. Genetic- and gender-based differences in the effects of SGAs have previously been reported [46]. Plasma concentration of antipsychotic drugs has shown to produce varied results based on age and gender.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population

et al. 2019

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Objectives: The aim of this study was to determine the incidence of metabolic syndrome in patients treated with second-generation antipsychotics (SGAs). Methods: In this retrospective study, we reviewed patients’ electronic medical records (EMRs) of all patients who received one SGA for at least six months, excluding patients who were taking other medications that are associated with significant effect on metabolic syndrome. Relevant clinical information was collected prior to starting the SGA and after six months of continuous use of the same SGA. Results: A total of 91 patients were included in the study. The majority of patients (72%) were diagnosed with schizophrenia. After six months of taking the SGA, 44% of patients experienced elevated systolic pressure, 54.9% had elevated triglyceride, and 31.9% had impaired glucose levels (p value < 0.05). Prior to initiating SGA therapy, 14.3% of patients had metabolic syndrome, while 37.4% had metabolic syndrome after six months of therapy, and it was more prominent in males compared to female patients (p value < 0.05). Conclusion: This study found a strong correlation between SGA use and the appearance of metabolic alterations, such as weight gain, glucose intolerance, and increased triglyceride levels. These findings highlight the importance of assessing metabolic deregulations to minimize SGA associated metabolic abnormalities.

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Section: Discussionmentioning

confidence: 99%

The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population

et al. 2019

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“…An association between MetS and HT2RC has also been proposed in other studies. For example, the rs498177 variant showed a significant association with MetS in female patients treated with olanzapine or risperidone [168], and the same was found for the rs518147CC and rs12836771GG variants in patients [169]. Although the contribution of HT2RC to MetS can be because of AIWG, we cannot rule-out the dysregulation of glucose metabolism.…”

Section: New Insights Into the Molecular Mechanisms By Which Sgas mentioning

confidence: 98%

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Grajales

Ferreira

Valverde

2019

Cells

109

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Second-generation antipsychotics (SGAs) are the cornerstone of treatment for schizophrenia because of their high clinical efficacy. However, SGA treatment is associated with severe metabolic alterations and body weight gain, which can increase the risk of type 2 diabetes and cardiovascular disease, and greatly accelerate mortality. Several underlying mechanisms have been proposed for antipsychotic-induced weight gain (AIWG), but some studies suggest that metabolic changes in insulin-sensitive tissues can be triggered before the onset of AIWG. In this review, we give an outlook on current research about the metabolic disturbances provoked by SGAs, with a particular focus on whole-body glucose homeostasis disturbances induced independently of AIWG, lipid dysregulation or adipose tissue disturbances. Specifically, we discuss the mechanistic insights gleamed from cellular and preclinical animal studies that have reported on the impact of SGAs on insulin signaling, endogenous glucose production, glucose uptake and insulin secretion in the liver, skeletal muscle and the endocrine pancreas. Finally, we discuss some of the genetic and epigenetic changes that might explain the different susceptibilities of SGA-treated patients to the metabolic side-effects of antipsychotics.

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“…A number of studies have found that the mutation of HTR2C is correlated with AIWG. [3][4][5][6] The -759 C/T polymorphism is located at the promoter region of HTR2C and associated with the ability to bind the transcription factor, affecting the expression of gene production. 21 This article has unprecedentedly used the complete Chinese database and conducted analyses on the correlation between HTR2C-759C/T and AIWG by using evidence-based medicine methods.…”

Section: Main Findingsmentioning

confidence: 99%

“…Furthermore, 5-HT2CR-deficient mice adopted an abnormal control of feeding behaviour, resulting in obesity and hyperglycaemias. [4][5][6] Taken together, previous genetic studies have found that a constellation of single-nucleotide polymorphisms in HTR2C is related to AIWG; the relationship between the -759 C/T (rs3813929) polymorphism and AIWG is an active field of research, but the results are controversial. Two earlier metaanalyses 7 8 ignored a number of studies in China; therefore, we performed a metaanalysis applying both English and Chinese databases to assess whether HTR2C -759 C/T is associated with AIWG.…”

Section: Introductionmentioning

confidence: 99%

Association of the HTR2C-759C/T polymorphism and antipsychotic-induced weight gain: a meta-analysis

et al. 2020

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BackgroundAntipsychotic-induced weight gain (AIWG) is a crucial factor for the medication cessation of patients with schizophrenia. Multiple studies have shown that the functional polymorphism -759 C/T (rs3813929) in the HTR2C promoter region could possibly be correlated with AIWG.AimTo evaluate the genetic association of the HTR2C-759C/T polymorphism and AIWG in patients with schizophrenia with antipsychotic drugs (APDs) administration.MethodsEligible studies were identified by searching the following databases: PubMed, Embase, Web of Science, China Nation Knowledge Infrastructure (CNKI), VIP, Wanfang Data, Chinese Biomedical Literature Database (CBM) and the Airiti Library. The quality of studies was evaluated based on the Newcastle-Ottawa Scale. The pooled OR and 95% CI were calculated for the dominant (CT/TT/T vs CC/C) mode, and subgroup analyses were performed based on ethnicity, antipsychotic medication and gender; all statistical analyses were performed using the statistical software STATA V.12.0.ResultA total of 17 studies with 3170 patients with schizophrenia were included in our meta-analysis. The result of the meta-analysis has shown that the association between the -759 C/T polymorphism and AIWG is statistically significant (OR 0.34, 95% CI: 0.20 to 0.57, z=4.11, p<0.001). The subgroup analyses revealed significant correlations between the -759 C/T polymorphism and AIWG in the Caucasian population (OR 0.33, 95% CI: 0.14 to 0.77, z=2.55, p=0.011), the Asian population (OR 0.31, 95% CI: 0.18 to 0.52, z=4.46, p<0.001), the patients with APDs administration (CT/TT/T vs CC/C: OR 0.63, 95% CI: 0.40 to 1.00, z=1.97, p=0.049) and the patients with atypical antipsychotic drug administration (CT/TT/T vs CC/C: OR 0.21, 95% CI: 0.09 to 0.47, z=3.83, p<0.001). The sensitivity analysis showed that the results were stable. Begg’s test (after correction z=1.07, p=0.287) and Egger’s test (t=−2.41, p=0.029) show that the included articles have no significant publication bias.ConclusionThere is a significant genetic association between HTR2C-759C/T and AIWG, and patients with T allele are less likely to have AIWG.

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Genetic polymorphisms of HTR2C, LEP and LEPR on metabolic syndromes in patients treated with atypical antipsychotic drugs

Cited by 16 publications

References 32 publications

The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population

The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Association of the HTR2C-759C/T polymorphism and antipsychotic-induced weight gain: a meta-analysis

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