Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms? Jesu li olanzapinom prouzročene promjene jetrenih enzima povezane s polimorfizmima gena GSTT1, GSTM1, GSTP1 i OGG1?

ELKAMA A., İlik N., Ak M., KARAHALİL B.

Arhiv za Higijenu Rada i Toksikologiju, cilt.75, sa.1, ss.61-67, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 75 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.2478/aiht-2024-75-3770
  • Dergi Adı: Arhiv za Higijenu Rada i Toksikologiju
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, Greenfile, Pollution Abstracts, SportDiscus, Veterinary Science Database, Directory of Open Access Journals
  • Sayfa Sayıları: ss.61-67
  • Anahtar Kelimeler: ALT, AST, drug-induced liver injury, mental disorders, psychotropic drugs, α-GST
  • Gazi Üniversitesi Adresli: Evet

Özet

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.