AUTHOR=Fan Yao , Gao Jun , Li Yinghui , Chen Xuefei , Zhang Ting , You Weiyan , Xue Yong , Shen Chong 

TITLE=The Variants at APOA1 and APOA4 Contribute to the Susceptibility of Schizophrenia With Inhibiting mRNA Expression in Peripheral Blood Leukocytes

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.785445

DOI=10.3389/fmolb.2021.785445

ISSN=2296-889X

ABSTRACT=<p><bold>Objective:</bold> Abnormal lipid metabolism has a close link to the pathophysiology of schizophrenia (SZ). This study mainly aimed to evaluate the association of variants at apolipoprotein A1 (<italic>APOA1</italic>) and <italic>APOA4</italic> with SZ in a Chinese Han population.</p><p><bold>Methods:</bold> The rs5072 of <italic>APOA1</italic> and rs1268354 of <italic>APOA4</italic> were examined in a case–control study involving 2,680 patients with SZ from the hospital and 2,223 healthy controls screened by physical examination from the community population. The association was estimated with the odds ratio (OR) and 95% confidence intervals (95% CIs) by logistic regression. The <italic>APOA1</italic> and <italic>APOA4</italic> messenger RNA (mRNA) in peripheral blood leukocytes were measured by real-time PCR and compared between SZ cases and controls. Serum apoA1 levels were detected by turbidimetric inhibition immunoassay and high-density lipoprotein cholesterol (HDL-C) levels were detected by the homogeneous method.</p><p><bold>Results:</bold> Both of the rs5072 of <italic>APOA1</italic> and rs1268354 of <italic>APOA4</italic> had statistically significant associations with SZ. After adjustment for age and sex, ORs (95% CIs) of the additive model of rs5072 and rs1268354 were 0.82 (0.75–0.90) and 1.120 (1.03–1.23), and <italic>p</italic>-values were 3.22 × 10<sup>−5</sup> and 0.011, respectively. The association of rs5072 with SZ still presented statistical significance even after Bonferroni correction (<italic>p</italic>-value×6). SZ patients during the episode presented lower levels of apoA1, HDL-C, mRNA of <italic>APOA1</italic> common variants and transcript variant 4, and <italic>APOA4</italic> mRNA than controls (<italic>p</italic> &lt; 0.01) while SZ patients in remission showed a significantly decreased <italic>APOA1</italic> transcript variant 3 expression level and increased <italic>APOA4</italic> mRNA expression level (<italic>p</italic> &lt; 0.01). mRNA expression levels of <italic>APOA1</italic> transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (<italic>p</italic><sub>trend</sub> = 0.017). After the SZ patients received an average of 27.50 ± 9.90 days of antipsychotic treatment, the median (interquartile) of serum apoA1 in the SZ episode significantly increased from 1.03 (1.00.1.20) g/L to 1.08 (1.00.1.22) g/L with the <italic>p</italic>-value of 0.044.</p><p><bold>Conclusion:</bold> Our findings suggest that the genetic variations of <italic>APOA1</italic> rs5072 and <italic>APOA4</italic> rs1268354 contribute to the susceptibility of SZ, and the expression levels of <italic>APOA1</italic> and <italic>APOA4</italic> mRNA of peripheral blood leukocytes decreased in SZ patients during the episode while <italic>APOA4</italic> increased after antipsychotic treatment.</p>