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

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.Schizophrenia (SZ) is a severe brain disorder afflicting approximately 1% of the world's population and often leads to a lifetime of disability and emotional distress [1]. Family, twin, and adoption studies strongly indicate that genetics contribute to the etiology of SZ, probably by transmission of multiple susceptibility genes each exerting weak-to-moderate effects on predisposition [2,3]. Many candidate susceptibility genes have been identified, including the dopamine receptor D2, neuregulin1, and disrupted in schizophrenia 1 (DISC-1) [4-6].Epidemiological studies have also revealed that people with SZ are at greater risk for obesity, type 2 diabetes, dyslipidemia, and hypertension than the general population [7]. Recently, it was suggested that SZ patients are at increased risk of metabolic problems and tha