Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation

Al-Riyami, Intisar; Al-Khabori, Murtadha; Balushi, Khalid Al; Al-Zadjali, Shoaib; Al-Rawahi, Mohammed; Dennison, David; Al-Hunaini, Mohammed; Al‐Rawas, Abdulhakim; Al-Moundhri, Mansour

doi:10.1097/ftd.0000000000000957

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Thus, the homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft‐versus‐host disease (GVHD) in BMT (hematopoietic stem cell allotransplantation [HSCT]). GSTM1 and double nonnull GSTT1 also increased mortality risk, concluding that GST genotyping prior to HSCT can predict HSCT results (Al‐Riyami et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

“…and double nonnull GSTT1 also increased mortality risk, concluding that GST genotyping prior to HSCT can predict HSCT results (Al-Riyami et al, 2022).…”

Section: Gstt1 Null Homozygote Mutated Totalmentioning

confidence: 95%

“…This gene is located on human chromosome 22q11.2, comprises five exons and is 8 kb long (Kerb et al., 2002; Nakanishi et al., 2022). Several diseases have been associated with gene expression and/or polymorphism of the GSTT1 enzyme, and they include pathologies such as sensitivity to mutagens, Type 2 diabetes mellitus, senile cataract, different carcinomas or de novo autoimmune hepatitis, among others (Al‐Riyami et al., 2022; Ansari‐Lari et al., 2020; Liu et al., 2022; Nassereddine et al., 2021; Nelson et al., 1995; Sobha & Ebenezar, 2021; Stepanova et al., 2021). Moreover, GSTT1 is also involved in activating the p38/MAPKAP kinase 2 (MK2) signal pathway.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of null deletion polymorphism of glutathione S‐transferase theta (GSTT‐1), associated with anti‐GSTT‐1 antibodies development in transplantation

Muro‐Perez,

González‐Martínez,

Martínez‐García

et al. 2023

Int J Immunogenetics

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Glutathione S‐transferase theta 1 (GSTT1) is an enzyme involved in phase II biotransformation processes and a member of a multigene family of detoxifying and clearing reactive oxygen species. GSTT1 is polymorphic like other biotransforming enzymes, allowing variability in hepatic conjugation processes. Immunological recognition of the GSTT1 alloantigen, as evidenced by donor‐specific antibodies formation, has previously been observed in recipients lacking GSTT1 protein (called GSTT1−, GSTT*0, null phenotype or homozygous for the GSTT1 deletion) who receive liver or kidney transplants from GSTT1+ donors and is a risk factor for the development of de novo hepatitis following liver transplants from a GSTT1 expressing donor. Antibodies against GSTT1 are demonstrated in patients who are GSTT1 null and received a transplant from a GSTT1+ donor. Understanding the local population frequency of the GSTT1 deletion is of value in understanding the potential clinical risk of developing post‐transplant complications, which can be attributed to the nonexpression of GSTT1. A population of 173 healthy donors of the Murcia Region in Southeast Spain was evaluated for a null allele of GSTT1 (n = 173). DNA was extracted, and GSTT‐1 null allele detection was performed by real‐time polymerase chain reaction. The frequency of the null GSTT1 genotype (nonexpression or deletion of the homozygous polymorphism of the GSTT1 protein) was 17.9% (n = 31 null allele GSTT1/173 total individuals). Our data suggest that the frequency of null GSTT1 mutations in our population in Southeast Spain is 17.9%, lower than in other Caucasoid populations. This would convert our recipient population into more susceptible to nonlocal potential organ donors and less susceptible to local donors. All recipients bearing this GSTT1 deletion homozygous would be without the protein and triggering an alloantigen in the case of transplantation with a donor without deletion.

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Section: Discussionmentioning

confidence: 99%

“…and double nonnull GSTT1 also increased mortality risk, concluding that GST genotyping prior to HSCT can predict HSCT results (Al-Riyami et al, 2022).…”

Section: Gstt1 Null Homozygote Mutated Totalmentioning

confidence: 95%