Chronic insomnia in the setting of MTHFR polymorphism

J Clin Sleep Med. 2022 Apr 1;18(4):1215-1218. doi: 10.5664/jcsm.9794.

Abstract

We present a patient with chronic insomnia resistant to traditional pharmacologic (eg, sedative-hypnotics) and nonpharmacologic (eg, cognitive behavioral therapy for insomnia) therapy. A finding of elevated serum homocysteine triggered a whole-genome sequencing analysis which revealed a homozygous methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T/C677T; dbSNP rs1801133). Interventions targeting her polymorphism-dependent loss of function successfully resolved her insomnia. This case demonstrates a genomic approach for insomnia whereby successful treatment was focused on optimizing the patient's metabolome, which was altered as a result of a missense single-nucleotide polymorphism.

Citation: Kapoor V, Watson NF, Ball L. Chronic insomnia in the setting of MTHFR polymorphism. J Clin Sleep Med. 2022;18(4):1215-1218.

Keywords: MTHFR single-nucleotide polymorphism; gene reversal; genomic approach; in-born error of metabolism; melatonin; metabolome; treatment-resistant insomnia; whole-genome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Polymorphism, Single Nucleotide
  • Sleep Initiation and Maintenance Disorders* / complications
  • Sleep Initiation and Maintenance Disorders* / genetics
  • Sleep Initiation and Maintenance Disorders* / therapy

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)