Genetics
A CETP variant is significantly associated with pentosan polysulfate (Elmiron) maculopathy, a genetic study of a drug-induced retinal disease finds (Retina 2023)
Original title: PENTOSAN POLYSULFATE SODIUM (ELMIRON) MACULOPATHY: A Genetic Perspective
A study of 15 patients (11 women, mean age 69) with maculopathy linked to pentosan polysulfate sodium (Elmiron) tested for inherited retinal dystrophy genes by exome sequencing and for 14 age-related macular degeneration (AMD) risk SNPs by panel testing, alongside full-field electroretinograms. Exome testing in five patients found six pathogenic variants but did not confirm a Mendelian inherited retinal dystrophy in any patient. Electroretinograms showed nonspecific abnormalities in 11 of 12 patients tested and were normal in one. Among AMD-associated SNPs, CFH rs3766405 (P = 0.003) and a CETP variant (P = 0.027) were significantly associated with the pentosan polysulfate maculopathy phenotype compared with controls. The authors conclude AMD risk alleles, including in CETP, may contribute to susceptibility to this drug-induced maculopathy via the alternative complement pathway, a genetic association study, not a CETP inhibitor safety finding, but relevant background for the CETP-AMD genetic debate.
Original abstract
Purpose: To assess genetic associations for pentosan polysufate sodium maculopathy.
Methods: Genetic testing for inherited retinal dystrophy genes using exome testing and for 14 age-related macular degeneration-associated single nucleotide polymorphisms (SNPs) using panel testing were performed. In addition, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy.
Results: Eleven of 15 patients were women, with a mean age of 69 (range 46-85). Inherited retinal dystrophy exome testing in five patients revealed six pathogenic variants, but failed to confirm inherited retinal dystrophy in any patient genetically. FfERG performed in 12 patients demonstrated only nonspecific a- and b-wave abnormalities in 11 cases and was normal in one case. For age-related macular degeneration single nucleotide polymorphisms, CFH rs3766405 ( P = 0.003) and CETP ( P = 0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared with the control population.
Conclusion: Pentosan polysulfate maculopathy is not associated with Mendelian inherited retinal dystrophy genes. However, several age-related macular degeneration risk alleles were identified to be associated with maculopathy compared with their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.