Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-23T12:28:42.344Z Has data issue: false hasContentIssue false

A genetic study of steroid-resistant nephrotic syndrome: relationship between polymorphism -173 G to C in the MIF gene and serum level MIF in children

Published online by Cambridge University Press:  06 November 2015

O. R. Ramayani*
Affiliation:
Department of Pediatrics, Sumatera Utara University, Medan, North Sumatera, Indonesia
N. Sekarwana
Affiliation:
Department of Pediatrics, Padjajaran University, Bandung, West Java, Indonesia
P. P. Trihono
Affiliation:
Department of Pediatrics, Indonesia University, Jakarta, Indonesia
A. H. Sadewa
Affiliation:
Department of Biochemistry, Gadjah Mada University, Jogjakarta, Indonesia
A. Lelo
Affiliation:
Department of Pharmacology and Therapeutics, Sumatera Utara University, Medan, North Sumatera, Indonesia
*
*Address for correspondence: O. R. Ramayani, Department of Pediatrics, University of North Sumatera, Bunga Lau Street, Medan, North Sumatera 20215, Indonesia. (Email [email protected])

Abstract

There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 μg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme-linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Berdeli, A, Mir, S, Ozkayin, N, et al. Association of macrophage migration inhibitory factor -173 C allele polymorphism with steroid resistance in children with nephrotic syndrome. Pediatr Nephrol. 2005; 20, 15661571.CrossRefGoogle ScholarPubMed
2. Vivarelli, M, D’Urbano, LE, Stringini, G, Ghiggeri, GM, Caridi, G. Association of macrophage migration inhibitory factor -173C allele with childhood nephrotic syndrome. Pediatr Nephrol. 2008; 23, 743748.CrossRefGoogle Scholar
3. ISKDC. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr. 1981; 98, 561564.Google Scholar
4. Schwartz, GJ, Haycock, GB, Edelmann, CM, Spitzer, A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976; 58, 259263.Google Scholar
5. Hogg, RJ, Furth, S, Lemley, KV, et al. National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification and stratification. Pediatrics. 2003; 111, 14161421.Google Scholar
6. R&D Systems, USA. Quantikine ELISA. Human MIF Immunoassay. Catalogue number DMF008 lot 294789. R&D Systems, Inc. Minneapolis, United States of America.Google Scholar
7. Yende, C, Angus, DC, Kong, L, et al. The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia. FASEB J. 2009; 23, 24032411.CrossRefGoogle ScholarPubMed
8. Renner, P, Roger, T, Bochud, PY. A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease. FASEB J. 2012; 26, 907916.Google Scholar
9. Shastry, BS. SNPs in disease gene mapping, medicinal drug development and evolution. J Hum Genet. 2007; 52, 871880.Google Scholar
10. Che, R, Zhang, A. Mechanism of glucocorticoid resistance in idiopathic nephrotic syndrome. Kidney Blood Press Res. 2013; 37, 360378.CrossRefGoogle ScholarPubMed
11. Mathieson, PW. Immune dysregulation in minimal change nephropathy. Nephrol Dial Transplant. 2003; 18, 2629.Google Scholar
12. Donnely, SC, Bucala, R. Macrophage pigration inhibitory factor: a regulator of glucocorticoid activity with a critical role in inflamatory disease. Mol Med. 1997; 502507.Google Scholar
13. Petrovsky, N, Socha, L, Silva, D, et al. Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter regulator. Immunol Cell Biol. 2003; 81, 137143.Google Scholar
14. Lan, HY. Role of macrophage migration inhibition factor in kidney disease. Nephron Exp Nephrol. 2008; 109, e79e83.Google Scholar
15. Van Rossum, EF, Lamberts, SW. Glucocorticoid resistance syndrome a diagnostic and therapeutic approach. Best Pract Res Clin Endocrinol Metab. 2006; 20, 611626.Google Scholar
16. Calandra, T, Roger, T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003; 3, 10381048.Google Scholar
17. Rice, EK, Tesch, GH, Cao, Z, et al. Induction of MIF synthesis and secretion by tubular epithelial cells: a novel action of angiotensin II. Kidney Int. 2003; 63, 12651275.Google Scholar
18. Murea, M, Register, TC, Divers, J, et al. Relationship between serum MCP-1 and subclinical kidney disease. BMC Nephrol. 2012; 13, 148164.Google Scholar