Association of the STAT4, CDKN1A, and IRF5 variants with risk of lupus nephritis and renal biopsy classification in patients in Vietnam

Abstract

Background Lupus nephritis is a common complication of systemic lupus erythematosus (SLE, OMIM #15200) in the Asian population and a main contributor to mortality and morbidity. In this study, we evaluate the variants on three genes STAT4, CDKN1A, and IRF5 and their association with lupus nephritis. Method One hundred fifty‐two SLE patients with confirmed lupus nephritis (through biopsy) and 76 healthy controls were recruited. Genotyping of SNPs on three gene STAT4, CDKN1A, and IRF5, phenotypic, and laboratory assessment were performed; renal biopsy and classification were carried out for the patient group. Results Carriers of rs7582694 C alleles on STAT4 have higher risk of lupus nephritis (OR 2.0; 95% CI [1.14, 3.19]; p = 0.015), at higher risk of hematuria and higher serum level of dsDNA antibodies compared to controls (p < 0.05) and were more likely to have nephrotic histopathology grading of class III or higher. No association was observed for CDKN1A; and no variation was observed for the IRF5 gene in both the study and control group. Conclusion This study investigates the relationship between STAT4, CDKN1A, and IRF5 gene and SLE in a Vietnamese patient population. Patients with the C allele (STAT4) in rs7582694 were associated with a more severe disease phenotype.

Identification and Validation of IFI44 as Key Biomarker in Lupus Nephritis

“…Additionally, antiviral genes such as ISG15, MX1, and the OAS gene family are involved in the pathogenesis of LN ( 23 ). Likewise, type I interferon signaling pathway-related genes, such as IRF5 and STAT4, are associated with the risk of LN ( 24 ). Triantafyllopoulou A et al revealed the role of intrarenal type I IFNs in kidney damage of LN ( 25 ).…”

Deciphering the Genetic Code of Autoimmune Kidney Diseases

“…Polymorphisms that affect the interferon signalling pathway are also associated with LN, such as the interferon γ (IFNG) gene and signal transducer and activator of transcription 4 (STAT4). The relationship between STAT4 and LN was demonstrated in a Vietnamese cohort, where a significant difference of p = 0.015 was observed in the distribution of the STAT4 genotype at position rs7582694 in SLE patients with LN compared to controls [53]. One study showed a stronger association in SNP rs11889341 with LN amongst a Swedish cohort, with p = 3.7 × 10 −9 [24].…”

Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy

“…In LN, abnormal interferon signaling and dysregulated IRFs have been linked to immune system hyperactivity and kidney inflammation. IRFs are involved in the pathogenesis of LN, and polymorphisms of IRF3, IRF5, and IRF7 are associated with LN [22,23]. MRL/lpr.IRF1-KO mice showed decreased inflammatory mediator production, decreased nephritis, and increased survival compared to MRL/lpr.IRF1-sufficient mice.…”