Association between Ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients

Yongfeng Yang,Weihua Yue,Dai Zhang,Luxian Lv,Ge Yang,Bo Xiao,Wenqiang Li,Xueqin Song,Jingyuan Zhao,Chengdi Jiang,Hongxing Zhang

doi:10.1186/1744-9081-8-11

Abstract

BackgroundGhrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response.MethodsFour SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects.ResultsThere were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05).ConclusionsThese four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

Highlights

Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass
There was no significant association between any allele or genotype and SZ when patients were subdivided by gender (Table 3)
The results revealed that there were no significant differences in positive and negative symptom scale scores (PANSS) score reduction among the different genotypes of the four Single nucleotide polymorphisms (SNPs) (-604 G/A, -501A/C, Leu72Met and -1062 G > C) after 8 weeks treatment with atypical antipsychotics (AAPs) (Table 6)

Summary

Introduction

Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). It is unclear whether GHRL polymorphisms are associated with WG due to AAPs. there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. Significant weight gain is common in AAP-treated SZ patients, especially patients administered clozapine, olanzapine, quetiapine, or risperidone [9]

Methods

Results

Conclusion