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

Behavioral and Brain Functions

Yongfeng Yang²  Wenqiang Li²  Jingyuan Zhao¹  Hongxing Zhang²  Xueqin Song³  Bo Xiao²  Ge Yang²  Chengdi Jiang²  Dai Zhang⁴  Weihua Yue⁴  Luxian Lv² 

[1] Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China

[2] Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, China

[3] First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

[4] Key Laboratory for Mental Health, Ministry of Health, Institute of Mental Health, Peking University, Beijing, China

关键词: Therapeutic effects;    Atypical antipsychotics;    Body mass index (BMI);    Polymorphrism;    Ghrelin (GHRL);    Schizophrenia;   

Others  :  797547
DOI  :  10.1186/1744-9081-8-11

 received in 2011-04-10, accepted in 2012-02-28,  发布年份 2012

【 摘 要 】

Background

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). 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.

Methods

Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects.

Results

There 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).

Conclusions

These 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.

【 授权许可】

   
2012 Yang et al; licensee BioMed Central Ltd.

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