Demontis Ditte, Nyegaard Mette, Christensen Jane H, Severinsen Jacob, Hedemand Anne, Hansen Thomas, Werge Thomas, Mors Ole, Børglum Anders D
Department of Human Genetics, Aarhus University, Århus, Denmark.
Psychiatr Genet. 2012 Apr;22(2):62-9. doi: 10.1097/YPG.0b013e32834dc424.
The MCHR1 gene encoding the melanin-concentrating hormone receptor 1 is located on chromosome 22q13.2 and has previously been associated with schizophrenia in a study of cases and controls from the Faroe Islands and Scotland. Herein we report an association between variations in the MCHR1 gene and schizophrenia, based on analyses of a larger sample and an increased number of single nucleotide polymorphisms (SNPs) than used in the previous study.
Eighteen SNPs in the MCHR1 gene region were genotyped in a Caucasian case-control sample from Denmark consisting of 390 individuals with schizophrenia and 814 control individuals. Sex-specific analysis and analysis of association with antipsychotic treatment were performed.
Five SNPs in the proximal region of MCHR1 were significantly associated with schizophrenia. The associations seemed to be sex specific, predominantly seen in men where one SNP (rs133073) remained significant (P=0.003) after correction for multiple testing. When combining the P values in the proximal region of MCHR1, the region-wise P value was low (P=0.009) supporting that variations in this part of the gene is associated with schizophrenia. Furthermore, the association was stronger in patients responding to conventional and atypical antipsychotic medication except clozapine.
Our results suggest that MCHR1 may influence schizophrenia susceptibility, in particular among men and patients responding to conventional (nonclozapine) treatment.
编码促黑素聚集激素受体1的MCHR1基因位于22号染色体q13.2区域,在一项针对法罗群岛和苏格兰的病例与对照的研究中,该基因先前已被发现与精神分裂症有关。在此,我们基于对更大样本的分析以及比先前研究中更多的单核苷酸多态性(SNP),报告MCHR1基因变异与精神分裂症之间的关联。
在一个来自丹麦的白种人病例对照样本中,对MCHR1基因区域的18个SNP进行基因分型,该样本包括390名精神分裂症患者和814名对照个体。进行了性别特异性分析以及与抗精神病药物治疗的关联分析。
MCHR1近端区域的5个SNP与精神分裂症显著相关。这些关联似乎具有性别特异性,主要见于男性,其中一个SNP(rs133073)在多重检验校正后仍具有显著性(P = 0.003)。当合并MCHR1近端区域的P值时,区域P值较低(P = 0.009),支持该基因这部分的变异与精神分裂症有关。此外,在对除氯氮平以外的传统和非典型抗精神病药物有反应的患者中,这种关联更强。
我们的结果表明,MCHR1可能影响精神分裂症易感性,尤其是在男性和对传统(非氯氮平)治疗有反应的患者中。