Methionine sulfoxide reductase A (MsrA) associated with bipolar I disorder and executive functions in A Han Chinese population

J Affect Disord. 2015 Sep 15;184:235-8. doi: 10.1016/j.jad.2015.06.004. Epub 2015 Jun 14.


Background: The oxidative stress hypothesis proposed to explain bipolar I disorder (BD I) pathogenesis has gained growing attention based on its association with cognitive impairment. The aim of the present study was to explore the association of the methionine sulfoxide reductase A (MsrA) gene with BD I as well as executive functions of BD I patients.

Methods: A total of 44 tagging single-nucleotide polymorphisms within the MsrA gene were selected to analyze gene association with BD I in 375 BD I patients and 475 controls in a Han Chinese population. The association of MsrA haplotypes with executive functions was analyzed in 157 clinically stable BD I patients and 210 controls.

Results: Allele frequencies of the rs4840463 polymorphism were significantly different between BD I patients and controls, and between patients with psychotic symptoms and controls. BD I patients performed more poorly in 11 of the 13 neurocognitive measurements compared with controls. Three MsrA haplotypes showed significant associations with different executive functions.

Limitations: The limited sample size requires a cautious conclusion, and further comprehensive approaches are needed to explore the mechanism of MsrA's effect on BD I.

Conclusions: The rs4840463 polymorphism in the MsrA gene may be associated with the increased risk of BD I in a Chinese population. The association of MsrA haplotypes with executive functions indicated that MsrA is associated with executive function defects in BD I patients.

Keywords: Bipolar I disorder (BD I); Executive functions; Methionine sulfoxide reductase A (MsrA); Psychotic symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics*
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology*
  • Case-Control Studies
  • China
  • Executive Function*
  • Female
  • Gene Frequency
  • Haplotypes
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Methionine Sulfoxide Reductases / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Young Adult


  • Methionine Sulfoxide Reductases
  • methionine sulfoxide reductase