Journal article 365 views
Deletion of CH25H and LIPA Genes in Human Abolishes Biosynthesis of 25-Hydroxycholesterol but not of 7α,25-Dihydroxysterols and Enhances Non-enzymatic Cholesterol Oxidation: Metabolic Changes are Partially Reversed by Hematopoieti...
Eylan Yutuc 
,
Arunabha Ghosh ,
Jonas Abdel-Khalik,
Anu Goenka ,
Mohsen Ali Asgari,
Gloria Lopez-Castejon ,
Glenda M Beaman ,
Robert F Wynn ,
William G Newman ,
Simon A Jones ,
William Griffiths ,
Yuqin Wang
,
Arunabha Ghosh ,
Jonas Abdel-Khalik,
Anu Goenka ,
Mohsen Ali Asgari,
Gloria Lopez-Castejon ,
Glenda M Beaman ,
Robert F Wynn ,
William G Newman ,
Simon A Jones ,
William Griffiths ,
Yuqin Wang
medRxiv
Swansea University Authors:
Eylan Yutuc , Jonas Abdel-Khalik, Mohsen Ali Asgari, William Griffiths , Yuqin Wang
Full text not available from this repository: check for access using links below.
DOI (Published version): 10.1101/2025.07.29.25330953
Abstract
The CH25H (cholesterol 25-hyroxylase) and LIPA (lipase A, lysosomal acid type) genes are contiguousgenes on chromosome 10. CH25H is translated to cholesterol 25-hydroxylase which generates 25-hydroxycholesterol (25-HC) from cholesterol, while LIPA codes for lysosomal acid lipase (LAL) whichhydrolyse...
| Published in: | medRxiv |
|---|---|
| Published: |
Cold Spring Harbor Laboratory
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa70079 |
| Abstract: |
The CH25H (cholesterol 25-hyroxylase) and LIPA (lipase A, lysosomal acid type) genes are contiguousgenes on chromosome 10. CH25H is translated to cholesterol 25-hydroxylase which generates 25-hydroxycholesterol (25-HC) from cholesterol, while LIPA codes for lysosomal acid lipase (LAL) whichhydrolyses cholesteryl esters in the endosome – lysosome compartment. Here we report the effecton the oxysterol pattern in plasma of the homozygous deletion of these two genes and theirrestoration by allogeneic hematopoietic stem cell transplant (HSCT). In the absence of CH25H, 25-HCis not detected in plasma, but surprisingly, 7α,25-dihydroxysterols are present, indicating theirformation by a second sterol 25-hydroxylase. As with the isolated deletion of LIPA seen in Wolmandisease, patients with the homozygous contiguous deletion show high levels of cholesterolautoxidation products in plasma. HSCT of patients with the contiguous deletion restores both 25-HCand autoxidation products to normal levels following an initial burst in autoxidation soon aftertransplant. |
|---|---|
| Item Description: |
Preprint article before certification by peer review. |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
BB/I001735/1, BB/N015932/1,
BB/S019588/1, MR/X012387/1, MR/Y008057/1 and BB/L001942/1 |