PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME

Damanhouri, Zoheir A.; Ali, Ahmed S.; AlAama, Jumana Y.; Almaweri, Fuad Y.; Khedr, Alaa M.; Khan, Lateef M.

doi:10.21608/bfsa.2020.127418

PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME

Document Type : Original Article

Authors

¹ Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia

² Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia & Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt

³ Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University (KAU), Saudi Arabia

⁴ Departmentt of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University (KAU), Saudi Arabia

10.21608/bfsa.2020.127418

Abstract

Background: Down syndrome (DS); a common chromosomal abnormality in humans can affect multiple organ systems. DS individuals usually use a wide range of medications. There is a gap in knowledge about the extent of contribution of CYP3A4/5 in altered clinical response to medications in DS children.
Objectives: Phenotyping of CYP3A4/5 in DS children using. the ratio of 4β-hydroxycholesterol / Cholesterol (4β-OHC/C) as an endogenous biomarker for CYP3A4/5 activity.
Method: The study was an observational case control study, conducted in the DS clinic, King Abdul-Aziz University Hospital. Blood samples were taken for thyroid and liver function test by automated immunoassay procedure and analysis of cholesterol and 4β-hydroxycholesterol by gas chromatography.
Results: 16 DS and 29 non-DS children were enrolled (1-12 Y). Children with DS showed a lower median 4β-OHC/C molar ratio of 0.19×10^-4compared to 0.45×10^-4in the control group and with interquartile range (IQR) 0.17, 0.36 respectively (p < 0.001 Mann Whitney U test). DS children also showed an abnormality in liver enzymes and hypercholesteremia.
Conclusion: Children with DS had about two-fold lower CYP3A4/5 activity compared to children without DS. More studies to confirm these observations are required, however, drugs should be used cautiously in DS children.