title: Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients.
abstract: 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.
authors.affiliation: Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Li
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Zhao
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.forename: Xueqin
authors.initials: X
authors.lastname: Song
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Ge
authors.initials: G
authors.lastname: Yang
authors.forename: Chengdi
authors.initials: C
authors.lastname: Jiang
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.forename: Luxian
authors.initials: L
authors.lastname: Lv
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D054439:Ghrelin / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D018401:Sample Size; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D054439:Ghrelin; D004247:DNA