CACNA1C Polymorphism (rs2283291) Is Associated with Schizophrenia in Chinese Males: A Case-Control Study.

Xiaojing Zhu,Yaoyao Sun,Qiong Yu,Yueying Wang,Mingyuan Zhang,Bonan Cao,Xin Chen,Guojun Kang,Rixin Li,Qi Kang,Yaqin Yu,Mingjia Yang,Wenwang Rao

doi:10.1155/2019/8062397

Abstract

Recent research has shown that prenatal famine exposure may be one of the risk factors for schizophrenia and that people born in famine years may be at an increased risk of schizophrenia due to alteration of the DNA methylation of genes. In this study, the association of rs2283291/rs4648635 and the incidence of schizophrenia and prenatal famine exposure at the genetic level were investigated to provide clues to the pathogenesis of schizophrenia. A total of 960 participants were recruited, comprising 473 prenatal famine-exposed individuals (225 patients and 248 controls) and 487 prenatal non-famine-exposed individuals (220 patients and 267 controls). The association of prenatal famine, schizophrenia, and their interaction with DNA methylation levels was analyzed using SPSS and GMDR software. Gender stratification analysis revealed a significant association between the rs2283291 genotype and schizophrenia in male patients (P = 0.017), and difference still existed after correction by the Bonferroni method. It was also found that an increasing risk of schizophrenia was associated with rs2283291 in males (OR: 1.62, 95% CI: 1.13-2.33, P = 0.0086, AIC = 669.7) in an overdominant model. The results of gene-environment interaction and gene-gene interaction revealed no association with the risk of schizophrenia. This study reported for the first time that rs2283291 was associated with schizophrenia in Chinese males.

Highlights

Schizophrenia (SCZ) is a serious mental illness with a lifetime prevalence of approximately 1%, with symptoms of affective disorder, cognitive disorder, and volitional behavior disorder [1], and its etiology is complex and involves genetic and environmental factors
Exposure to famine during pregnancy has a serious impact on the development of the foetus, and maternal protein deficiency especially methionine and folic acid deficiency can cause DNA methylation changes [5, 6]; folic acid is a key component of DNA methylation [7], and insufficient dietary supplementation of methionine, folic acid, vitamin B6, etc., can alter DNA methylation, thereby changing an offspring’s phenotype
This study explores the association between DNA methylationrelated sites and the incidence of SCZ as well as the effect of famine exposure at the genetic level, providing clues to reveal the pathogenesis of SCZ

Summary

Introduction

Schizophrenia (SCZ) is a serious mental illness with a lifetime prevalence of approximately 1%, with symptoms of affective disorder, cognitive disorder, and volitional behavior disorder [1], and its etiology is complex and involves genetic and environmental factors. DNA methylation plays a vital role in SCZ and can directly act as a pathogenesis or biomarker of SCZ [2]. Exposure to famine during pregnancy has a serious impact on the development of the foetus, and maternal protein deficiency especially methionine and folic acid deficiency can cause DNA methylation changes [5, 6]; folic acid is a key component of DNA methylation [7], and insufficient dietary supplementation of methionine, folic acid, vitamin B6, etc., can alter DNA methylation, thereby changing an offspring’s phenotype. Retrospective studies have revealed that a poor utero environment caused by famine during pregnancy can lead to differences in DNA methylation in offspring [8]. People born during famine years may have altered DNA methylation due to nutrient deficiency

Methods

Results

Conclusion