Yonsei Med J.  2017 May;58(3):619-625. 10.3349/ymj.2017.58.3.619.

Gender-Specific Associations between CHGB Genetic Variants and Schizophrenia in a Korean Population

Affiliations
  • 1Department of Life Science, Sogang University, Seoul, Korea. hdshin@sogang.ac.kr
  • 2Research Institute for Basic Science, Sogang University, Seoul, Korea.
  • 3Department of Psychiatry, College of Medicine, Gyeongsang National University, Jinju, Korea.
  • 4Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju, Korea.
  • 5Department of Neuropsychiatry, Hallym University Hangang Sacred Heart Hospital, Seoul, Korea.
  • 6Department of Neuropsychiatry, Soonchunhyang University Hospital, Seoul, Korea. siwoo@schmc.ac.kr
  • 7Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.

Abstract

PURPOSE
Schizophrenia is a devastating mental disorder and is known to be affected by genetic factors. The chromogranin B (CHGB), a member of the chromogranin gene family, has been proposed as a candidate gene associated with the risk of schizophrenia. The secretory pathway for peptide hormones and neuropeptides in the brain is regulated by chromogranin proteins. The aim of this study was to investigate the potential associations between genetic variants of CHGB and schizophrenia susceptibility.
MATERIALS AND METHODS
In the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls.
RESULTS
Statistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3"²-untranslated region) were associated with schizophrenia [minimum p=0.002; odds ratio (OR)=0.72], even after correction for multiple testing (p(corr)=0.02). Since schizophrenia is known to be differentially expressed between sexes, additional analysis for sex was performed. As a result, these two genetic variants (rs910122 and rs2821) and a haplotype (ht3) showed significant associations with schizophrenia in male subjects (p(corr)=0.02; OR=0.64), whereas the significance disappeared in female subjects (p>0.05).
CONCLUSION
Although this study has limitations including a small number of samples and lack of functional study, our results suggest that genetic variants of CHGB may have sex-specific effects on the risk of schizophrenia and provide useful preliminary information for further study.

Keyword

Single nucleotide polymorphisms; chromogranin B; schizophrenia; gender-specific marker

MeSH Terms

Adult
Asian Continental Ancestry Group/*genetics
Brain/*metabolism/physiopathology
Case-Control Studies
Chromogranin B/*genetics
Female
Genetic Markers/genetics
Genetic Predisposition to Disease/*genetics
Genotype
Haplotypes
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide/*genetics
Republic of Korea/epidemiology
Schizophrenia/ethnology/*genetics
Sex Factors
Chromogranin B
Genetic Markers

Figure

  • Fig. 1 Schematic physical map of CHGB. (A) Polymorphisms of CHGB investigated in this study. Black blocks indicate coding exons; white blocks, 5′- and 3′-untranslated regions. First base of translation site is denoted as nucleotide +1. (B) LDs among CHGB polymorphisms. (C) Haplotypes (hts) of CHGB in a Korean population. CHGB, chromogranin B; LD, linkage disequilibrium.


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