Gender-Specific Associations betweenCHGBGenetic Variants and Schizophrenia in a Korean Population

Abstract

PurposeSchizophrenia 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 MethodsIn the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls.ResultsStatistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3′-untranslated region) were associated with schizophrenia [minimum p=0.002; odds ratio (OR)=0.72], even after correction for multiple testing (pcorr=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 (pcorr=0.02; OR=0.64), whereas the significance disappeared in female subjects (p>0.05).ConclusionAlthough 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.

Association Between Polymorphisms of the Complement 3 Gene and Schizophrenia in a Han Chinese Population

“…Weiss’s group [17] indicated that several variants of SHANK3 had associations with SCZ. Gender-specific associations between variants of CHGB and SCZ have been revealed in a Korean population by Shin et al [15]. Conversely, a case-control study indicated that there was no significant association between SNPs of FGA and SCZ [19].…”

“…Over the past few decades, variants in several candidate genes, including DRD2 , ZNF804A , CHGB , NRGN , SHANK3 , BACE1 , FGA , and complement 3 ( C3 ), were found to be associated with SCZ [15-20]. Particularly, the concentration of C3 in the blood of patients with SCZ has been extensively studied, and the role of complement in SCZ is beginning to be more widely explored.…”

Selected neuropeptide genes show genetic differentiation between Africans and non-Africans

“…All five SNPs were associated with stress that arises due to changes in blood pressure in Southern Californians, including sub-Saharan African and European ancestry groups [33]. Moreover, two SNPs (rs6085324 and rs742711) have been associated with schizophrenia in the Korean population [19] and SNP rs236152 has also been associated with schizophrenia in the Japanese population [16].…”

“…Even so, the knowledge available on the variability and expression pattern of these neuropeptide genes in different modern human populations is limited at the moment. The majority of the studies conducted on these genes [13][14][15] so far have tended to focus on one specific neuropeptide in one specific population [11,[16][17][18][19].…”

NG2 Glia: Novel Roles beyond Re-/Myelination

“…in adult mouse NG2 glia [169] Modulation of neuronal activity [170] Chromogranin B, Chgb Gene expr. study of freshly sorted adult human NG2 glia [125] Neurotransmission [171,172] Chromogranin C, Chgc Gene expr. study of freshly sorted adult human NG2 glia [125] Neurite outgrowth [173] and angiogenesis [174].…”