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Relationship between the C3435T and G2677A/T single nucleotide polymorphisms of the P-glycoprotein in the mdr-1 gene and efavirenz plasma concentration in patients with HIV infection

Abstract number: 1733_1398

Peralta G., Sanchez M.B., Valdizan E., Echevarria S., Nicolás J., Segura R., Badía V., Armijo J.A.

Objectives: P-glycoprotein is a drug transporter recognized to be important to drug disposition and response. This protein is of particular clinical relevance due to a broad substrate specificity and expression in multiple tissues. The C3435T AND G2677A/T single nucleotide polymorphisms (SNPs) have been associated with altered transporter function or expression (higher function/expression of P-glycoprotein for CC or GG genotypes, and less for TT genotype). Its role in antiretroviral drug pharmacokinetics is still to be clarified.

Methods: For the study we selected 40 patients in treatment with Efavirenz (600 mg qd) for at least six weeks. We analysed the relationship between the C3435T and G2677A/T SNPs genotypes and efavirenz plasma concentrations twelve hours after oral administration. We excluded those patients in treatment with other drugs with potential interaction with Efavirenz. The genotypes were determined with the use of polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) assays and with allelic discrimination by PCR assays. Efavirenz plasma levels were measured by high pressure liquid chromatography. To compare means an ANOVA and t-test were used.

Results: For the 40 patients studied, the genotype distribution was: CC: 25%, CT: 52.5%, TT: 20%, for the C3435T SNP; and GG: 35%, GT: 55%, TT: 10% for the G2677A/T SNP. We did not find a statistically significant difference between the C3435T SNP genotypes and efavirenz plasma concentrations (CC: 1.73±0.80 mg/L; CT: 3.11±2.42 mg/L; TT: 2.63±1.24 mg/L). But when we compared patients with genotype CC with patients with genotype CT and TT all together, the difference tended to significance (P = 0.083). We did find statistically significant difference between the G2677A/T SNP genotypes and efavirenz plasma concentrations (GG: 1.62±0.76 mg/L; GT: 3.20±2.28 mg/L; TT: 3.13±1.60 mg/L; P = 0.047).

Conclusions: Although the sample is small, in our patients the efavirenz concentrations seems to be in relation with the G2677A/T SNP, and probably with C3435T SNP too. These data have to be confirmed in a bigger group of patients.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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