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Association of Retinoid X Receptor Alpha Gene Polymorphism with Clinical Course of Chronic Glomerulonephritis

Alicja E. Grzegorzewska, Grzegorz Ostromecki, Paulina Zielińska, Adrianna Mostowska, Zofia Niemir, Magdalena Polcyn-Adamczak, Magdalena Pawlik, Anna Sowińska, Paweł P. Jagodziński

(Department of Nephrology, Transplantology and Internal Diseases, Poznań University of Medical Sciences, Poznań, Poland)

Med Sci Monit 2015; 21:3671-3681

DOI: 10.12659/MSM.895249

Published: 2015-11-27

BACKGROUND: Vitamin D (VD), VD binding protein, VD receptor (VDR), and retinoids are involved in pathogenesis of chronic glomerulonephritis (ChGN). We aimed to compare distribution of VD pathway gene polymorphisms in ChGN patients showing glomerular filtration rate (GFR) category 1-3, GFR category 5D, and healthy controls in order to elucidate the role of VD-related polymorphisms in the course of ChGN.
MATERIAL AND METHODS: GFR category 1–3 ChGN patients (n=195), GFR category 5D ChGN patients (n=178), and controls (n=751) underwent testing for polymorphisms of genes encoding VD binding protein (GC, rs2298849, rs7041, rs1155563), VDR (VDR, rs2228570, rs1544410), and retinoid X receptor alpha (RXRA, rs10776909, rs10881578, rs749759).
RESULTS: Among GFR 1–3 subjects possessing TT genotype of RXRA rs10776909, 75% of patients had nephrotic syndrome, and 37.5% had glomerular hyperfiltration defined as GFR >140 ml/min/1.73 m2, and, consequently, serum creatinine was lower in these patients compared to the remaining subjects (0.67±0.26 vs. 0.94±0.34, P=0.014). In GFR category 5D ChGN patients, frequencies of RXRA rs10776909 allele T (25% vs. 19%) and CT+TT (46% vs. 34%) were higher compared to frequencies of respective variants in controls (Ptrend=0.004, Pgenotype=0.008).
CONCLUSIONS: RXRA rs10776909 allele T is specifically involved in the pathogenesis of ChGN. This risk allele may be also associated with worse clinical course of ChGN.

Keywords: Aged, Adult, Adolescent, Alleles, Case-Control Studies, Chronic Disease, Female, Gene Frequency, Genetic Predisposition to Disease, Glomerulonephritis - therapy, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Calcitriol - metabolism, Renal Dialysis, Retinoid X Receptor alpha - metabolism, Vitamin D - metabolism, Vitamin D-Binding Protein - metabolism, young adult