Background: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight\r\ngain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin\r\npolymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure,\r\nplasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated\r\nwith WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ\r\nor the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ\r\npatients and controls. We also examined the relation between these SNPs and changes in metabolic indices during\r\nAAP treatment in SZ subgroups distinguished by high or low therapeutic response.\r\nMethods: Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia\r\npatients and 606 control subjects.\r\nResults: There were no significant differences in allele frequencies, genotype distributions, or the distributions of\r\ntwo SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference\r\nin symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative\r\nsymptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase\r\nin response to AAP administration in both APP responders and non-responders as distinguished by PANSS score\r\nreduction (P < 0.001). There were also significant differences in WG when the responder group was further\r\nsubdivided according to the specific AAP prescribed (P < 0.05).\r\nConclusions: These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604\r\nG/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting\r\nhigher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower\r\nweight gain or weight loss.
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