Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms

Mong Liang Lu, Wei Chi Ku, Nailis Syifa, Shu Chin Hu, Chia Te Chou, Yi Hsio Wu, Po Hsiu Kuo, Chun Hsin Chen, Wei J. Chen, Tzu Hua Wu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC–MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 μL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.

Original languageEnglish
Article number3320
Issue number16
Publication statusPublished - Aug 2022


  • 5-methyltetrahydrofolate
  • LC–MS/MS
  • MTHFR C677T
  • PON1 Q192R
  • schizophrenia

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics


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