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Effect of GSTP1 polymorphism on efficacy and safety of cyclophosphamide aggressive therapy in lupus nephropathy patients

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Abstract

Background

Lupus nephritis (LN) occurs in up to 60% of adults with systemic lupus erythematosus (SLE) and is a predictor of poor survival. Cyclophosphamide (CYC) is regarded as the most effective immunosuppressive medication to improve survival for patients with LN.

Objective

This prospective hospital-based study was conducted to identify the effect of glutathione S transferase Pi-1 (GSTP1) genotypes on the efficacy and safety of CYC aggressive therapy.

Methods

We enrolled SLE nephropathy patients admitted to the Department of Rheumatology of the 500-bed Yangon Specialty Hospital (YSH), Yangon, Myanmar, who received CYC aggressive therapy for 6 months according to treatment guidelines for SLE patients with renal involvement. The frequencies of I/I, I/V and V/V GSTP1 genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism method. The efficacy of CYC aggressive therapy between LN patients with wild GSTP1 (I/I) and those with polymorphic GSTP1 (I/V or V/V) genotypes was evaluated by comparing 24-h urinary protein levels and assessing the remission rates at 3 and 6 months after initiation of CYC. CYC-related myelotoxicity was assessed by reviewing complete blood picture results on the 10th day after CYC treatment.

Results

In total, 95 eligible patients were recruited. The frequencies of I/I, I/V and V/V GSTP1 genotypes were 54.7, 41.1 and 4.2%, respectively. At 3 and 6 months after CYC treatment, mean 24-h urinary protein had significantly decreased from baseline in both wild and polymorphic genotype groups (p < 0.001). No significant differences were seen between the wild and polymorphic genotype groups with regard to changes in 24-h urinary protein levels, remission at 3 and 6 months or myelotoxicity.

Conclusion

CYC aggressive therapy had similar efficacy and caused no significant differences in myelotoxicity in wild GSTP1 (I/I) and polymorphic GSTP1 (I/V or V/V) genotypes in patients treated according to YSH guidelines for SLE patients with renal involvement.

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Acknowledgements

The authors acknowledge the help and support of all the staff of the Department of Rheumatology, 500-bed Yangon Specialty Hospital and the Immunology Research Division of the Department of Medical Research, for their expert assistance.

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Authors and Affiliations

  1. Department of Pharmacology, University of Medicine 1, Yangon, No. 245, Myoma Kyaung Street, Lanmadaw Township, Yangon, Myanmar

    K. Khine Thu, Khin Mar Myint, Ye Htut Linn & Nang Hla Hla Win

  2. Department of Medical Research, Ministry of Health and Sports, Yangon, Myanmar

    Aye Aye Lwin & Khin Than Maw

  3. 500-Bed Yangon Specialty Hospital, Yangon, Myanmar

    Lei Lei Htay & Chit Soe

  4. Department of Pharmacology, University of Medicine Magway, Magway, Myanmar

    Myat Myat Soe

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  1. K. Khine Thu
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  2. Aye Aye Lwin
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Corresponding author

Correspondence to Ye Htut Linn.

Ethics declarations

Ethical approval

This study was approved by the Research and Ethics Committee of University of Medicine 1, Yangon, and was registered at Thai Clinical Trial registry with the trial registration number TCTR20180828012. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individuals participating in the study.

Conflicts of interest

K Khine Thu, Aye Aye Lwin, Khin Than Maw, Lei Lei Htay, Khin Mar Myint, Myat Myat Soe, Ye Htut Linn, Chit Soe, and Nang Hla Hla Win have no conflicts of interest that are directly relevant to the content of this article.

Funding

No sources of funding were used to conduct this study or prepare this manuscript.

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Thu, K.K., Lwin, A.A., Maw, K.T. et al. Effect of GSTP1 polymorphism on efficacy and safety of cyclophosphamide aggressive therapy in lupus nephropathy patients. Drugs Ther Perspect 35, 334–340 (2019). https://doi.org/10.1007/s40267-019-00631-x

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  • DOI: https://doi.org/10.1007/s40267-019-00631-x

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