Alleles of CYP3A5 and their association with renal function in chronic kidney disease

The cytochrome P450 family 3 subfamily A polypeptide 5 (CYP3A5) gene plays an important role in renal function through its product's involvement in metabolizing endogenous substances and drugs, including immunosuppressants used following kidney transplantation. A single-nucleotide polymorphism, CYP3A5*3 (rs776746), produces a non-functional variant that may influence progression of chronic kidney disease (CKD) by impairing renal filtration. However, the frequency of the CYP3A5*3 allele in the Thai population and its association with renal parameters remain underexplored. This study aimed to determine the prevalence of CYP3A5 polymorphisms and their association with renal function.

We investigated the distribution of CYP3A5 polymorphisms in 329 northeastern Thai participants, including 205 CKD patients and 124 healthy controls. Genotyping was performed using the TaqMan allelic discrimination assay. Renal function parameters were assessed and compared between CYP3A5*1 and CYP3A5*3 allele carriers.

In the entire cohort, the allele frequency of CYP3A5*3 was 63.2%, with genotype frequencies of CYP3A5*1/*1 (16.7%), CYP3A5*1/*3 (40.1%), and CYP3A5*3/*3 (43.2%). There was no significant difference in the CYP3A5 allele frequencies between CKD and control groups. CYP3A5*3 carriers exhibited significantly lower eGFR, urine creatinine and serum creatinine clearance and higher UACR compared to CYP3A5*1 carriers. After adjusting for confounders, CYP3A5*3 remained significantly associated with reduced urine creatinine.

This study highlights a high prevalence of CYP3A5 polymorphisms in the northeastern Thai population. The association of the CYP3A5*3 allele with renal function parameters underscores the need for further research into the mechanisms by which CYP3A5 affects kidney function, which could inform personalized CKD management strategies.