Authors of a pharmacogenomic study investigated whether genetic differences could help predict glucocorticoid response in patients with high-risk IgA nephropathy (IgAN). In a genome-wide analysis of 260 Chinese participants from the TESTING trial, researchers identified several genetic signals associated with changes in proteinuria after methylprednisolone treatment. The strongest and most consistent finding involved the rs477155 variant: patients with the GG genotype had 2.5-fold higher odds of complete proteinuria remission, while combined complete or partial remission increased from 19% in patients with the AA genotype to 67% in those with the GG genotype.
The rs477155 association was also replicated in an independent cohort of 211 patients, where each G allele was associated with greater proteinuria reduction and GG carriers had 1.8-fold higher odds of complete remission. Functional analyses suggest the variant may influence glucocorticoid response through regulation of the CDA gene and glucocorticoid receptor signaling. However, rs477155 did not reach conventional genome-wide significance, the discovery cohort was relatively small. Both cohorts consisted of patients who were Chinese, so larger multiethnic studies are needed before genetic testing could be used to guide treatment decisions.
Reference: Xu LL, Zhou XJ, Bi W, et al. Genetic Determinants of Steroid Responsiveness in IgA Nephropathy. J Am Soc Nephrol. 2026 Jun 1;37(6):1248-1260. doi: 10.1681/ASN.0000000977.
