MI,11 while mineral bone disorders, including secondary hyperparathyroidism (HPT), were reported as more severe in uremic women than in men. [12][13][14] Sex-specific effects of vitamin D were also demonstrated in mice. 15Decreased plasma 25(OH)D levels may be caused by insufficient levels of circulating vitamin D-binding protein (DBP), which has a spectrum of biological activities (actin scavenging, fatty acid transport, macrophage activation, and chemotaxis) and transports vitamin D to its receptors in target tissues.16 Lower baseline plasmais a widely accepted biomarker of the vitamin D status, also in end-stage renal disease (ESRD). 1 Patients with ESRD, including those on hemodialysis (HD), usually have low plasma vitamin D levels. 2,3Vitamin D deficiency is epidemiologically linked to life-threatening diseases such as myocardial infarction (MI), 4-6 cerebral stroke, 5 and bone fractures, 7 the prevalence of which is related to sex. 4,[8][9][10] In dialysis patients, the above conditions are more frequent than in the general population. Male sex was shown to be associated with a higher frequency of OBJECTIVES We evaluated the frequency distribution of GC polymorphic variants in hemodialysis (HD) patients and healthy subjects as well as the differences in the prevalence of coronary artery disease (CAD) and myocardial infarction (MI) and selected clinical and laboratory indices of secondary hyperparathyroidism in HD patients (women and men) with different GC polymorphic variants.PATIENTS AND METHODS HD patients (n = 1056; 625 men) and healthy controls (n = 313; 150 men) were enrolled into the study. The tested GC polymorphisms included rs2298849, rs7041, and rs1155563. We analyzed clinical data (prevalence of CAD and MI; treatment with parathyroidectomy or cinacalcet) and laboratory results (serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxy vitamin D [25(OH)D) in relation to the gene polymorphisms.RESULTS There were no differences between the study groups themselves and between the study groups and controls in terms of the frequency distribution of GC polymorphisms (P trend <0.05). Lower plasma 25(OH)D levels were shown in subjects with the rs7041 TT genotype compared with those with the GG genotype (12.7, 5.7-20.9 ng/ml vs. 15.9, 8.0-50.0 ng/ml, P = 0.02). Women with the rs7041 TT genotype compared with those with the GG genotype showed higher serum phosphorus levels (5.58, 3.40-8.97 mg/dl vs. 5.03, 1.75-9.33 mg/dl, P = 0.007).CONCLUSIONS HD patients do not differ in the distribution of GC polymorphisms rs2298849, rs7041, and rs1155563 from healthy subjects. In HD patients, the GC polymorphism is associated with plasma 25(OH)D levels. Sex-related factors may be important in the expression of associations between GC polymorphic variants and mineral disorders.

Background. T-cell cytokine gene polymorphisms and vitamin D pathway gene polymorphisms were evaluated as possibly associated with end-stage renal disease (ESRD) resulting from type 2 diabetes mellitus (DM) nephropathy. Methods. Studies were conducted among hemodialysis (HD) patients with ESRD due to type 2 DM nephropathy, chronic glomerulonephritis, chronic infective tubulointerstitial nephritis, and hypertensive nephropathy as well as in healthy subjects. A frequency distribution of T-cell-related interleukin (IL) genes (IL18 rs360719, IL12A rs568408, IL12B rs3212227, IL4R rs1805015, IL13 rs20541, IL28B rs8099917, IL28B, and rs12979860) and vitamin D pathway genes (GC genes: rs2298849, rs7041, and rs1155563; VDR genes: rs2228570, rs1544410; and RXRA genes: rs10776909, rs10881578, and rs749759) was compared between groups. Results. No significant differences in a frequency distribution of tested polymorphisms were shown between type 2 DM nephropathy patients and controls. A difference was found in IL18 rs360719 polymorphic distribution between the former group and chronic infective tubulointerstitial nephritic patients (P trend = 0.033), which also differed in this polymorphism from controls (P trend = 0.005). Conclusion. T-cell cytokine and vitamin D pathway gene polymorphisms are not associated with ESRD due to type 2 DM nephropathy in Polish HD patients. IL18 rs360719 is probably associated with the pathogenesis of chronic infective tubulointerstitial nephritis.

BackgroundVitamin 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/MethodsGFR 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).ResultsAmong 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).ConclusionsRXRA rs10776909 allele T is specifically involved in the pathogenesis of ChGN. This risk allele may be also associated with worse clinical course of ChGN.

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