Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Behav Brain Funct. 2012 Feb 28;8:11. doi: 10.1186/1744-9081-8-11.
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.
Ghrelin（GHRL）是一种重要的肽类调节剂，可调节食物摄入、能量平衡和体重。体重增加（WG）是用于治疗精神分裂症（SZ）的非典型抗精神病药物（AAP）的常见副作用。Ghrelin 多态性与血浆脂质浓度、血压、血糖和体重指数（BMI）的致病性变化有关。然而，由于 AAP，Ghrelin 多态性是否与 WG 相关尚不清楚。此外，没有证据表明 GHRL 多态性与 SZ 或 AAP 的治疗反应有关。我们通过对 SZ 患者和对照组进行 GHRL 等位基因分型来探讨这些潜在的关联。我们还研究了这些 SNP 与 SZ 亚组在 AAP 治疗期间代谢指标变化之间的关系，这些亚组根据高或低治疗反应进行区分。
在 634 名精神分裂症患者和 606 名对照中，对 4 个 SNP（Leu72Met、-501A/C、-604G/A 和 -1062G>C）进行了基因分型。
SZ 患者和健康对照组之间的等位基因频率、基因型分布或两个 SNP 单倍型的分布没有显著差异（P>0.05）。在 8 周 AAP 治疗后，根据阳性和阴性症状量表评分（PANSS）衡量的症状改善，基因型之间也没有差异。然而，-604G/A 多态性与 AAP 治疗后 APP 应答者和非应答者的 BMI 增加显著相关，以 PANSS 评分降低为区分（P<0.001）。当根据特定的 AAP 处方进一步细分应答者组时，也存在 WG 方面的显著差异（P<0.05）。
在中国汉族人群中，这四个 GHRL 基因 SNP 与 SZ 无关。-604G/A 多态性与 AAP 治疗期间 BW 和 BMI 的显著增加有关。表现出更高 WG 的患者在阳性和阴性症状方面的改善程度大于体重增加或体重减轻的患者。
