XMN polymorphism along with HU administration renders alterations to RBC membrane lipidome in β-thalassemia patients.

Autor: Khan MBN; Dr.Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan., Iftikhar F; Dr.Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan., Ali M; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan., Danish A; National Institute of Blood Disease & Bone Marrow Transplantation, Karachi 75300, Pakistan., Shamsi T; National Institute of Blood Disease & Bone Marrow Transplantation, Karachi 75300, Pakistan., Musharraf SG; Dr.Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: musharraf@iccs.edu., Siddiqui AJ; Dr.Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: amna.jabbar@iccs.edu.
Jazyk: angličtina
Zdroj: Chemistry and physics of lipids [Chem Phys Lipids] 2022 May; Vol. 244, pp. 105195. Date of Electronic Publication: 2022 Mar 12.
DOI: 10.1016/j.chemphyslip.2022.105195
Abstrakt: RBCs membrane loses its integrity during hemoglobinopathies such as β-thalassemia and sickle cell disease. The severity of β-thalassemia has been historically linked to the presence of XMN polymorphism which is believed to ameliorate the severity. Here, we investigate the effect of XMN polymorphism on RBC membrane lipidome isolated from patients, using LC-MS/MS based approach. A total of 50 patients were recruited and 28 lipid species were identified in all groups after statistical analyses using volcano plot and ANOVA-SCA, and lipids with higher VIP values extracted from OPLS-DA loading plot. Alteration in lipid levels specifically the membrane lipids such as PC and fatty acids were observed. Samples with XMN polymorphism exhibited up-regulation of lipids involved in membrane stability such as cholenoic acid while PC (O-41:1) was down-regulated when compared to non-XMN samples. Additionally, HU administration to samples also had profound effect on the lipids of patients in both groups. A trend of improvement in the membrane lipids was observed in patients with XMN polymorphism. HU administration has proven to further improve the membrane integrity by upregulating certain membrane lipids in such patients. The study presents a comprehensive analysis of RBC membrane lipidome with respect to the genetic variation and HU administration.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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