Osteopontin Gene Polymorphism and Urinary OPN Excretion in Patients with Immunoglobulin A Nephropathy

Abstract

Osteopontin (OPN) is a glycoprotein involved in the pathogenesis of multiple autoimmune and inflammatory conditions. However, the association of variants of secreted phosphoprotein 1 gene (SPP1), which encodes OPN, with immunoglobulin A nephropathy (IgAN) has not been examined up to date. Moreover, the role of OPN in disease pathogenesis and clinical manifestations is not fully known. Therefore, the aim of the study was to determine the frequency of four single nucleotide polymorphisms (SNiPs) of SPP1 gene, as well as the urinary OPN excretion in IgAN patients and healthy controls. In total, 58 Caucasian patients with biopsy-proven IgAN and 184 gender-, age-, and ethnically-matched healthy controls were genotyped for rs1126616, rs1126772, rs9138, and rs7687316/rs3841116 polymorphisms by real time polymerase chain reaction (RT-PCR). Urinary OPN concentration was determined by enzyme-linked immunosorbent assay (ELISA) in 58 IgAN patients and 19 controls. SPP1 SNiPs, as well as urinary OPN excretion, were analyzed in relation to their possible associations with the clinicopathological parameters. The frequency of the minor TT/CT genotypes of rs1126616 was significantly higher in IgAN patients compared to controls (P = 0.0217). Similarly, the minor (CC/AC) genotypes and the C allele of rs9138 were more frequent in IgAN patients (P = 0.0425 and P = 0.0112, respectively). Moreover, these two SNiPs were associated with the higher urinary OPN excretion (P < 0.05). These findings suggest that rs1126616, as well as rs9138, may be associated with IgAN development, however future studies in this field are required.

Osteopontin—A Potential Biomarker for IgA Nephropathy: Machine Learning Application

“…However, OPN as a factor for discriminating between various kidney diseases has not yet been fully explored. In previous research, our team focused on the link between OPN gene polymorphisms and excretion of uOPN in patients with IgAN [9]. In the present study, we compared uOPN in various immune-related glomerulopathies.…”

“…The role of OPN in glomerular diseases is not clearly defined. OPN gene polymorphisms are associated with the development of diabetic nephropathy in type 2 diabetes [8], urinary OPN (uOPN) excretion in patients with IgA nephropathy (IgAN) [9], and acute renal allograft rejection [10]. OPN mRNA expression in tissue is increased in areas of tubular damage [11] and in patients with renal calculi [12].…”

Genetics of osteopontin in patients with chronic kidney disease: The German Chronic Kidney Disease study

“…In the past several specific SPP1 gene variants have been associated with the pathogenesis and progression of different kidney diseases. Other case-control studies reported on specific variants in the SPP1 gene being associated with different kidney disease patients in comparison to a (healthy) control group: For example, rs1126616 was repeatedly reported as a marker for lupus nephritis and immunoglobulin A nephropathy [ 10 – 14 ]. In connection with diabetic nephropathy, the two SNPs in SPP1 , rs11730582 and rs17524488, have been reported [ 15 , 16 ].…”

NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies

“…Both GNs are classified as rare diseases with ORPHA numbers 761 and 97560, respectively, without targeted treatment or prognostic markers, yet. Recent years have brought new insights into a molecular background of GNs, especially in the field of -omics (genomics, transcriptomics, and proteomics) [2][3][4][5][6][7]. These discoveries revealed pathophysiologic mechanisms, which could be helpful in the development of biomarkers and targeted therapy in the future.…”