Association betweenABCC2Gene Haplotypes and Tenofovir‐Induced Proximal Tubulopathy

Abstract

ABCC2 haplotypes are associated with rPT induced by TDF in HIV-1-infected patients.

Renal Vulnerability to Drug Toxicity

“…In the future, more information regarding how patients differ in the function and regulation of channels, transporters, and carriers that regulate elimination of drugs and other compounds cleared by the kidney will be brought to light. An elegant example of this is seen with tenofovir-induced Fanconi syndrome (32). In patients exposed to tenofovir who developed Fanconi syndrome, a single nucleotide polymorphism (1249 G3 A SNP) was present in the gene coding the multidrug-resistant protein-2 (MRP2) efflux transporter, which transports tenofovir out of the cell.…”

Screening study for genetic polymorphisms affecting pharmacokinetics of simvastatin

“…In another study, no association was observed between two non-synonymous and seven synonymous ABCC4 variants and tenofovir disoproxil fumarate-induced renal proximal tubulopathy. [32] Most recently, 74 genetic variants in ABCC4 were shown to have no effect on MRP4 mRNA and protein expression in Caucasian cholestatic and non-cholestatic patients. [33] However, they reported that ABCC4 genotype affected drug metabolism.…”

The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

“…Polymorphisms in SLC22A have been examined and no relationship with toxicity has been found [98,99], whereas, polymorphisms at the ABCC2 gene, which encodes for MRP2, has been associated with TFV renal damage. The haplotype "CATC" (defined as the combination of the polymorphisms at positions -24C>T, 1249G>A, 3563T>A and 3972C>T) [100] and the allele -24C [98] have been associated with an increased risk of TFV-associated kidney tubular dysfunction (KTD). Furthermore, MRP4 (encoded by ABCC4) [98,100] and MRP7 (encoded by ABCC10) [101] seem to play a role in the pathogenesis of KTD.…”

“…The haplotype "CATC" (defined as the combination of the polymorphisms at positions -24C>T, 1249G>A, 3563T>A and 3972C>T) [100] and the allele -24C [98] have been associated with an increased risk of TFV-associated kidney tubular dysfunction (KTD). Furthermore, MRP4 (encoded by ABCC4) [98,100] and MRP7 (encoded by ABCC10) [101] seem to play a role in the pathogenesis of KTD. A 669C>T polymorphism at the ABCC4 gene has been found to be more frequent in patients experiencing renal tubular damage [100] and another polymorphism within ABCC10 gene has been associated with urine phosphate wasting and β2-microglobulinuria, which are indicative of renal tubular dysfunction [101].…”

“…Furthermore, MRP4 (encoded by ABCC4) [98,100] and MRP7 (encoded by ABCC10) [101] seem to play a role in the pathogenesis of KTD. A 669C>T polymorphism at the ABCC4 gene has been found to be more frequent in patients experiencing renal tubular damage [100] and another polymorphism within ABCC10 gene has been associated with urine phosphate wasting and β2-microglobulinuria, which are indicative of renal tubular dysfunction [101]. Regardless of these associations, currently information about the effect of genetic polymorphisms on the risk of renal toxicity using TFV is a matter of controversy and requires further examination.…”