Association between KCNQ2, TCF4 and RGS18 polymorphisms and silent brain infarction based on whole‑exome sequencing

Mol Med Rep. 2020 Apr;21(4):1973-1983. doi: 10.3892/mmr.2020.10975. Epub 2020 Feb 5.


Silent brain infarction (SBI) is a cerebral infarction identified through brain imaging. In particular, studies have shown that the presence of SBI in elderly patients increases their risk of cognitive dysfunction, impairment and dementia. However, little research has been published on the relevance of SBI to these risks for the Korean population. The association between potassium voltage‑gated channel subfamily Q member 2 (KCNQ2), transcription factor 4 (TCF4) and regulator of G‑protein signaling 18 (RGS18) genotypes and SBI were investigated using whole‑exome sequencing and PCR restriction fragment length polymorphism (RFLP) analysis. The study population included 407 patients with SBI (171 males) and 401 control subjects (172 males). Genotyping was performed using PCR RFLP. Interestingly, TCF4 rs9957668T>C polymorphisms were associated with SBI prevalence [TT vs. CC: adjusted odds ratio (AOR), 1.815, 95% confidence intervals (CI), 1.202‑2.740; TT vs. TC+CC: AOR, 1.492, 95% CI, 1.066‑2.088; TT+TC vs. CC: AOR, 1.454, 95% CI, 1.045‑2.203]. The combination of KCNQ2 rs73146513A>G and TCF4 rs9957668T>C genotypes was associated with increasing SBI prevalence (AG/CC: AOR, 3.719, 95% CI, 1.766‑7.833; AA/CC: AOR, 3.201, 95% CI, 1.387‑7.387). The present study showed that TCF4 rs9957668T>C polymorphisms may be risk factors for SBI. Therefore, the TCF4 rs9957668T>C polymorphism may serve as a biomarker for increased risk of SBI in the Korean population.

Keywords: silent brain infarction; prevalence; risk factors; case‑control studies; single nucleotide polymorphism.

MeSH terms

  • Alleles
  • Brain Infarction / genetics*
  • Case-Control Studies
  • Exome Sequencing*
  • Female
  • Gene Frequency / genetics
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • KCNQ2 Potassium Channel / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • RGS Proteins / genetics*
  • Transcription Factor 4 / genetics*


  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • RGS Proteins
  • RGS18 protein, human
  • TCF4 protein, human
  • Transcription Factor 4