Article

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

Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Behavioral and Brain Functions (Impact Factor: 2.79). 02/2012; 8:11. DOI: 10.1186/1744-9081-8-11
Source: PubMed

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

0 Bookmarks
 · 
160 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antipsychotic medications are used to effectively treat various symptoms for different psychiatric conditions. Unfortunately, antipsychotic-induced weight gain (AIWG) is a common side effect that frequently results in obesity and secondary medical conditions. Twin and sibling studies have indicated that genetic factors are likely to be highly involved in AIWG. Over recent years, there has been considerable progress in this area, with several consistently replicated findings, as well as the identification of new genes and implicated pathways. Here, we will review the most recent genetic studies related to AIWG using the Medline database (PubMed) and Google Scholar. Among the steadiest findings associated with AIWG are serotonin 2C receptors (HTR2C) and leptin promoter gene variants, with more recent studies implicating MTHFR and, in particular, MC4R genes. Additional support was reported for the HRH1, BDNF, NPY, CNR1, GHRL, FTO and AMPK genes. Notably, some of the reported variants appear to have relatively large effect sizes. These findings have provided insights into the mechanisms involved in AIWG and will help to develop predictive genetic tests in the near future.
    Pharmacogenomics 12/2013; 14(16):2067-83. · 3.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is a severe disorder that significantly affects the quality of life and total functioning of patients and their caregivers. Clozapine is the first atypical antipsychotic with fewer adverse effects and established efficacy. As a rule of thumb, risperidone is one of the most reliable and effective antipsychotics for newly diagnosed and chronic schizophrenics. Pharmacogenetic studies have identified genomic variants of candidate genes that seem to be important in the way a patient responds to treatment. The recent progress made in pharmacogenomics will improve the quality of treatment, since drug doses will be tailored to the special needs of each patient. In this article, we review the available literature attempting to delineate the role of genomic variations in clozapine and risperidone response in schizophrenic patients of various ethnicities. We conclude that pharmacogenomics for these two drugs is still not ready for implementation in the clinic.
    Pharmacogenomics 01/2014; 15(1):95-110. · 3.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of studies have reported that patients with schizophrenia have a higher body mass index (BMI) than the general population. Few Asian studies have examined BMI in patients with schizophrenia. The aims of the current study were to evaluate the distribution of BMI and prevalence of obesity in a large sample of Chinese patients with schizophrenia (n = 973) and to examine the sociodemographic and clinical correlates of overweight (BMI ≥25 kg/m) and obesity (BMI ≥30 kg/m). There was a preponderance of patients who were overweight (58.7%) and obese (73.6%) as compared with control subjects. Regression modeling of clinical and symptom factors in schizophrenia patients revealed that females were almost twice as likely to be obese compared with males and patients with comorbid medical conditions were more likely to be obese compared with those who did not have a comorbid medical condition (odds ratio, 1.6). Those prescribed typical antipsychotic medications were 1.7 times more likely to be obese, whereas individuals prescribed with both typical and atypical antipsychotic medications were 2.2 times more likely to be obese as compared with those prescribed atypical antipsychotics. A significant predictor interaction for obesity was observed between sex and typical antipsychotics, sex and comorbid medical conditions, and years of education and comorbid medical conditions. The higher prevalence of obesity in patients with schizophrenia is a matter of clinical and public health concern; interventions to reduce weight to healthy levels would result in both improved health and quality of life among patients with schizophrenia.
    Journal of clinical psychopharmacology 12/2013; · 5.09 Impact Factor

Full-text (2 Sources)

View
7 Downloads
Available from
Jun 3, 2014