C677T Polymorphism in the MTHFR Gene Is Associated With Risperidone-Induced Weight Gain in Schizophrenia.

Jingping Liao,Weihua Yue,Ning Wang,Tianlan Lu,Mengying Ma,Hao Yan

doi:10.3389/fpsyt.2020.00617

Abstract

ObjectiveTo explore the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with risperidone-induced weight gain.MethodsWe analyzed the association between MTHFR C677T polymorphism and risperidone-induced weight gain in 356 schizophrenia patients. The patients were treated with risperidone for 8 weeks. The height and body weight of the patients were measured before and 8 weeks after risperidone treatment. Blood DNA was genotyped for MTHFR C677T polymorphisms.ResultsWe found a significant association between MTHFR C677T polymorphism and body mass index (BMI) change after 8-week risperidone treatment. The BMI of carriers with different genotypes of MTHFR gene increased over 2–8 weeks. After 8 weeks of risperidone treatment, BMI added value (kg/m2) of CC or CT genotype carriers was significantly higher than that of TT genotype carriers [CC (4.47 ± 1.09), CT (4.54 ± 1.27), TT (2.31 ± 0.75), F = 5.634, P = 0.001]. Based on whether the rate of weight gain from baseline at 8 weeks of treatment exceeded 7%, it was divided into a weight gain group (n = 61) and a non-weight gain group (n = 295). The C allele frequency was significantly different between the two groups (48.4% vs 32.4%, χ2 = 11.342, P = 0.001).Conclusion MTHFR C677T polymorphism was associated with risperidone-induced weight gain in Chinese Han population.

Highlights

Schizophrenia is a chronic, complex, and severe mental disorder, affecting approximately 1% of the general population
We examined the association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with risperidone-induced weight gain in patients with schizophrenia
According to the Hardy-Weinberg equilibrium (HWE), there was no significant difference between the observed value and expected value of genotype frequency for MTHFR C677T polymorphism

Summary

Introduction

Schizophrenia is a chronic, complex, and severe mental disorder, affecting approximately 1% of the general population. With the prevailing use of atypical antipsychotics or second-generation antipsychotics (SGAs), the adverse effects such as weight gain and metabolic abnormalities have become a major. Susceptibility to antipsychotic-induced weight gain varies substantially between individuals in ways that cannot be fully explained by differences in drug effects or other environmental factors. Genetic factors are strongly implicated, and researches have been conducted to find possible associations between many genetic polymorphisms and antipsychotic-induced weight gain [5]. The genetic factors which were commonly reported to be involved in antipsychotic-induced weight gain include polymorphisms in genes for HTR2C [6], 5-HT2A [7, 8], MC4R [9], Leptin [10], FTO [11], and BDNF [12]

Methods

Results

Conclusion