Epistatic interactions among CYP2C19*2, CYP3A4 and GSTP1 on the cyclophosphamide therapy in lupus nephritis patients.

Abstract

AIM:

To investigate the impact of genetic variants in CYP2C9, CYP2C19, CYP3A4, GSTT1, GSTM1 and GSTP1 on the efficacy of cyclophosphamide (CYC) therapy in patients with lupus nephritis.

MATERIALS & METHODS:

Lupus nephritis patients (n = 220) treated with CYC were included in the study.

RESULTS:

Logistic regression analysis identified CYP2C19*2 as an independent predictor of CYC therapeutic failure (odds ratio [OR]: 2.69; p = 0.0043). Bivariate and trivariate analysis showed the subjects harboring CYP2C19*2 and GSTP1 (OR: 3.25; p = 0.03), and CYP2C19*2, GSTP1 and CYP3A5*3 have synergistic influence on CYC failure (OR: 8.2; p < 0.0001). Significant decrease in AUC0-t, Cmax and t½ of 4-OH-CYC in patients carrying CYP3A5*3 (p < 0.02).

CONCLUSION:

Patients with CYP2C19*2 were at increased risk and CYP2C19*2, CYP3A5*3 and GSTP1 have synergistic influence on CYC failure.

• Authors: Konda Kumaraswami, Shiva Krishna Katkam, Amita Aggarwal, Aman Sharma, Ramesh Manthri, Vijay Kumar Kutala, Liza Rajasekhar
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 18 Issue 15 Pg. 1401-1411 (Oct 2017) ISSN: 1744-8042 [Electronic] England
• PMID: 28976264 (Publication Type: Journal Article)

Chemical References

• Cyclophosphamide
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Cytochrome P-450 CYP3A
• CYP3A4 protein, human
• GSTP1 protein, human
• Glutathione S-Transferase pi

Topics

• Adult
• Cyclophosphamide (therapeutic use)
• Cytochrome P-450 CYP2C19 (genetics)
• Cytochrome P-450 CYP3A (genetics)
• Female
• Glutathione S-Transferase pi (genetics)
• Humans
• Lupus Nephritis (drug therapy, genetics)
• Male
• Polymorphism, Single Nucleotide (genetics)
• Treatment Failure