Paraoxonase 1 gene (PON1) variants concerning hepatitis C virus (HCV) spontaneous clearance in hemodialysis individuals: a case-control study.

BACKGROUND: To explore associations between PON1 rs854560, rs662, 705,379, HCV clearance, and interactions between tested PON1 single nucleotide variants (SNVs) and interferon-λ4 gene (IFNL4) rs368234815 variant in hemodialyzed individuals. METHODS: The study included 83 HD individuals who spontaneously resolved HCV infection (all had known IFNL4 rs368234815 variant) and 104 individuals with persistently positive blood tests for HCV RNA (102 were IFNL4 rs368234815 variant successfully genotyped). We genotyped PON1 by high-resolution melt analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). We used a logistic regression model to assess the association between genetic data and HCV outcome while adjusting for clinical confounding variables. Epistatic interactions between tested PON1 SNVs and IFNL4 rs368234815 were analyzed by the multifactor dimensionality reduction method. RESULTS: In the recessive inheritance model, PON1 rs662 GG (OR 9.94, 95% CI 1.20-82.7, P = 0.022) and rs854560 TT (OR 4.31, 95% CI 1.62-11.5, P = 0.003) genotypes were associated with a higher probability for HCV clearance. The haplotype composed of rs662A_rs854560A_rs705379 was not associated with spontaneous HCV clearance. The IFNL4 rs368234815 TT/TT variant was equally distributed among individuals bearing different PON1 SNVs. The epistatic gene-gene analysis did not reveal the interaction between tested PON1 SNVs and IFNL4 rs368234815 (P = 0.094). Regression model, including the PON1 rs662 GG genotype, the PON1 rs854560 genotype, the IFNL4 rs368234815 TT/TT genotype, age at RRT onset, RRT duration, and chronic glomerulonephritis as possible explanatory variables for spontaneous HCV clearance, showed that significant predictors of spontaneous HCV clearance were the IFNL4 rs368234815 TT/TT genotype (OR 2.607, 95% CI 1.298-5.235, P = 0.007), PON1 rs854560 TT (OR 6.208, 1.962-19.644, P = 0.002), PON1 rs662 GG (OR 10.762, 1.222-94.796, P = 0.032), and RRT duration (OR 0.930, 95% CI 0.879-0.984, P = 0.011). CONCLUSION: In HD individuals, PON1 rs662 GG and rs854560 TT are associated with a higher frequency of spontaneous HCV clearance.

Polymorphism rs368234815 of interferon lambda 4 gene and spontaneous clearance of hepatitis C virus in haemodialysis patients: a case-control study.

BACKGROUND: In non-uremic subjects, IFNL4 rs368234815 predicts HCV clearance. We investigated whether rs368234815 is associated with spontaneous HCV clearance in haemodialysis patients and whether it is a stronger predictor of HCV resolution than the IFNL polymorphisms already associated with HCV clearance in dialysis subjects. We also evaluated an association of rs368234815 with patients` survival and alterations in transcription factor binding sites (TFBS) caused by IFNL polymorphisms. METHODS: Among 161 haemodialysis patients with positive anti-HCV antibodies, 68 (42.2%) spontaneously resolved HCV infection, whereas 93 remained HCV RNA positive. Patients were tested for near IFNL3 rs12980275, IFNL3 rs4803217, IFNL4 rs12979860, IFNL4 rs368234815, and near IFNL4 rs8099917. IFNL4 rs368234815 polymorphism (TT/TT, ΔG/TT, ΔG/ΔG) was genotyped by restriction fragment length polymorphism analysis; other IFNL polymorphisms - by high resolution melting curve analysis. We used the Kaplan-Meier method with the log-rank test for survival analysis. In silico analysis included the use of ENCODE TFBS ChIP-seq data, HOCOMOCO, JASPAR CORE, and CIS-BP databases, and FIMO software. RESULTS: The probability (OR, 95%CI, P) of spontaneous HCV clearance for rs368234815 TT/TT patients was higher than for the ΔG allele carriers (2.63, 1.38-5.04, 0.003). This probability for other major homozygotes varied between 2.80, 1.45-5.43, 0.002 for rs12980275 and 2.44, 1.27-4.69, 0.007 for rs12979860. In the additive model, rs368234815 TT/TT was the strongest predictor of HCV clearance (6.38, 1.69-24.2, 0.003). Survival analysis suggested an association of the ΔG allele with mortality due to neoplasms (log-rank P = 0.005). The rs368234815 ∆G allele caused TFBS removal for PLAGL1. CONCLUSIONS: In haemodialysis patients, the association of rs368234815 with the spontaneous HCV clearance is better than that documented for other IFNL3/IFNL4 polymorphisms only in the additive mode of inheritance. However, identifying the homozygosity in the variant ∆G allele of rs368234815 means a more potent prediction of persistent HCV infection in haemodialysis subjects that we observe in the case of the variant homozygosity of other tested IFNL3/IFNL4 polymorphisms. Removal of PLAGL1 TFBS in subjects harbouring the rs368234815 ∆G allele may contribute to cancer susceptibility. The association of rs368234815 with cancer-related mortality needs further studies in HCV-exposed subjects.

Exposure to hepatitis E virus in hemodialysis patients from west-central Poland.

Hepatitis E virus (HEV) causes travel-related but also locally acquired infections in industrialized parts of the world, including European countries. Food and blood transfusions are possible sources of transmission. Infections caused by zoonotic variants of the virus (particularly HEV-3) may progress to chronic liver disease in a nonnegligible proportion of immunocompromised people. The aim of this study was to assess the prevalence of serological markers of HEV infection in 189 patients on renal replacement therapy (RRT, currently on hemodialysis, HD) living in west-central Poland and to determine the factors related to HEV exposure in this group. Testing was carried out using commonly used commercial assays (Wantai Biological Pharmacy Enterprise Co, Beijing, China). Anti-HEV IgG was detected in 94 patients (49.7%); none of the participants had anti-HEV IgM or HEV Ag. Patients on RRT (HD) for less than 6 months were significantly more likely to be anti-HEV IgG-positive than dependent of RRT (HD) for more than half a year (80% vs 47%; P = .014). Exposure to HEV in patients from west-central Poland is frequent, but no clear sources of this infection have been identified. There were no serological features of ongoing liver disease caused by HEV in the study subjects.

Circulating interferon-λ3 and post-vaccination antibodies against the surface antigen of hepatitis B virus in hemodialysis patients exposed to hepatitis E virus.

Responsiveness to the hepatitis B virus (HBV) vaccination in hemodialysis (HD) patients who had been exposed to the hepatitis E virus (HEV) and persistently generate antibodies against HEV remains unknown. Interferon (IFN)-λ3 positively correlates with the surface HBV antibodies (anti-HBs) in both healthy and HD subjects. We aimed to show whether HD patients differ in circulating IFN-λ3 and vaccine-induced anti-HBs titers concerning natural HEV immunization. HBV/HCV negative HD patients (31 HEV IgG positive, 45 HEV negative), HBV vaccinated and receiving booster doses as needed, had been tested for anti-HBs titers (CMIA) and IFN-λ3 concentrations (ELISA) in the blood collected before a dialysis session. There were no differences in circulating IFN-λ3 and anti-HBs titers between both groups. In responders to the HBV vaccine, there was a positive correlation between plasma IFN-λ3 levels and anti-HBs titers (r = 0.505, adjusted P = 0.01 in HEV exposed subjects; r = 0.523, adjusted P = 0.001 in controls). HEV past infection does not attenuate post-vaccination anti-HBs generation and does not influence a correlation between circulating IFN-λ3 levels and anti-HBs titers.

Calcium-sensing receptor gene (CASR) polymorphisms and CASR transcript level concerning dyslipidemia in hemodialysis patients: a cross-sectional study.

BACKGROUND: There is scarce data on CASR associations with dyslipidemia. We investigated in hemodialysis (HD) patients whether CASR single nucleotide polymorphisms (SNPs) rs7652589 and rs1801725 have associations with dyslipidemia and show epistatic interactions with SNPs of the energy homeostasis-associated gene (ENHO), retinoid X receptor α gene (RXRA), and liver X receptor α gene (LXRA). METHODS: The study included 1208 HD subjects. For diagnosis of dyslipidemia, both K/DOQI criteria and atherogenic index ≥3.8 were used. CASR rs1801725 was genotyped by TaqMan SNP Genotyping Assay, other SNPs - by high-resolution melting curve analysis or polymerase chain reaction-restriction fragment length polymorphism, as appropriate. Relative transcript levels of CASR, ENHO, RXRA, and LXRA were measured in peripheral blood mononuclear cells. The occurrence of dyslipidemic phenotypes concerning tested polymorphisms was compared using models of inheritance. Haplotypes were estimated using the Haploview 4.2 software. Epistatic interactions between tested SNPs were analyzed using the logistic regression and epistasis option in the PLINK software. RESULTS: Rs7652589 indicated a greater probability of atherogenic dyslipidemia in the dominant inheritance model (OR 1.4, 95%CI 1.0-2.0, P = 0.026), principally because of increased triglyceride (TG) levels. The rs1801725 variant allele was associated with a decreased probability of dyslipidemia characterized by non-HDL-cholesterol ≥130 mg/dL and TG ≥200 mg/dL (OR 0.6, 0.4-0.9, P = 0.012). There were no epistatic interactions between CASR and RXRA, LXRA, and ENHO regarding dyslipidemia. Both rs7652589 and rs1801725 SNPs were not in linkage disequilibrium (D' = 0.091, r2 = 0.003 for the entire HD group) and their haplotypes did not correlate with dyslipidemia. Relative CASR transcript was lower at a borderline significance level in patients harboring the rs1801725 variant allele compared with homozygotes of the major allele (0.20, 0.06-7.80 vs. 0.43, 0.04-5.06, P = 0.058). CASR transcript correlated positively with RXRA transcript (adjusted P = 0.001), LXRA transcript (adjusted P = 0.0009), ENHO transcript (borderline significance, adjusted P = 0.055), dry body weight (adjusted P = 0.035), and renal replacement therapy duration (adjusted P = 0.013). CONCLUSIONS: CASR polymorphisms (rs7652589, rs1801725) are associated with dyslipidemia in HD patients. CASR correlates with RXRA, LXRA, and ENHO at the transcript level. Further investigations may elucidate whether other CASR SNPs contribute to associations shown in this study.

ENHO, RXRA, and LXRA polymorphisms and dyslipidaemia, related comorbidities and survival in haemodialysis patients.

BACKGROUND: The energy homeostasis-associated gene (ENHO), retinoid X receptor alpha gene (RXRA), and liver X receptor alpha gene (LXRA) are involved in adipogenic/lipogenic regulation. We investigated whether single-nucleotide polymorphisms in these genes (ENHO rs2281997, rs72735260; RXRA rs749759, rs10776909, rs10881578; LXRA rs2279238, rs7120118, rs11039155) are associated with dyslipidaemia, related comorbidities and survival of haemodialysis (HD) patients also tested for T-helper (Th) cell interleukin genes (IL). METHODS: The study was carried out in 873 HD patients. Dyslipidaemia was diagnosed by the recommendations of the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines (2003); atherogenic dyslipidaemia was referred to if the TG/HDL cholesterol ratio was equal to or higher than 3.8. Genotyping of ENHO SNPs, LXRA SNPs, and IL12A rs568408 was carried out using HRM analysis. RXRA SNPs, IL12B rs3212227, and IL18 rs360719 were genotyped using PCR-RFLP analysis. The circulating adropin concentration was determined in 126 patients by enzyme-linked immunosorbent assay. Survival probability was analysed using the Kaplan-Meier method in 440 patients followed through 7.5 years. RESULTS: Dyslipidaemia by K/DOQI was diagnosed in 459 patients (91% revealed hyper-LDL- cholesterolaemia), atherogenic dyslipidaemia was diagnosed in 454 patients, and 231 patients were free of dyslipidaemia by both criteria. The variant allele (T) of ENHO rs2281997 was associated with the hyper-LDL cholesterolaemic pattern of dyslipidaemia by K/DOQI. The frequency of atherogenic dyslipidaemia was lower in T-allele bearers than in CC-genotype patients. The rs2281997 T allele was associated with lower cardiovascular mortality in HD patients showing atherogenic dyslipidaemia. ENHO, RXRA, and LXRA showed epistatic interactions in dyslipidaemia. Circulating adropin was lower in atherogenic dyslipidaemia than in non-atherogenic conditions. RXRA rs10776909 was associated with myocardial infarction. Bearers of LXRA rs2279238, rs7120118 or rs11039155 minor alleles showed higher mortality. ENHO SNP positions fell within the same DNase 1 hypersensitivity site expressed in the Th1 cell line. Epistatic interactions occurred between rs2281997 and Th1 IL SNPs (rs360719, rs568408). CONCLUSIONS: Atherogenic dyslipidaemia occurs in HD patients in whom ENHO encodes less adropin. ENHO, RXRA, and LXRA SNPs, separately or jointly, are associated with dyslipidaemia, myocardial infarction, and survival in HD patients. Differences in the availability of transcription binding sites may contribute to these associations.

The Calcium-Sensing Receptor Gene Polymorphism rs1801725 and Calcium-Related Phenotypes in Hemodialysis Patients.

BACKGROUND/AIMS: The calcium-sensing receptor gene (CASR) rs1801725 variant is responsible for a non-conservative amino-acid change (A986S) in the calcium-sensing receptor cytoplasmic tail. We hypothesized that rs1801725 polymorphism might be helpful in understanding Ca-related abnormalities in HD patients. METHODS: In 1215 subjects (245 on cinacalcet), we determined the associations of rs1801725 with secondary hyperparathyroidism (sHPT)-related laboratory parameters, PTH-decreasing effect of cinacalcet hydrochloride, coronary artery disease (CAD), myocardial infarction (MI), nephrolithiasis-related ESRD, and mortality. CASR rs7652589(AT) haplotypes and rs1801725 epistatic interactions with vitamin D signaling pathway genes were examined for associations with selected phenotypes. RESULTS: The rs1801725 variant allele showed an increasing independent effect on plasma PTH (Pcorrected = 0.009). CASR rs7652589_rs1801725 AT haplotype was associated with 1.7-fold higher frequency of PTH levels over 437 pg/mL than the reference haplotype GG (P = 0.001). CASR rs7652589_rs1801725 AG haplotype was 1.5-fold more frequent in nephrolithiasis-related ESRD than the GG haplotype (P = 0.004). There were no significant associations between rs1801725, CAD, MI, and response to cinacalcet. Variant homozygosity of rs1801725 correlated independently with higher infection-related mortality compared with heterozygosity (HR 7.95, 95%CI 2.15 - 29.37, P = 0.003) and major homozygosity (HR 5.89, 95%CI 1.69 - 20.55, P = 0.040). CASR rs1801725 did not show epistatic interactions with vitamin D signaling pathway genes concerning tested associations. CONCLUSION: The variant allele of CASR rs1801725 solely and together with the variant allele of rs7652589 increases risk of more advanced sHPT. Homozygosity of the rs1801725 variant allele contributes to infection-related mortality in HD patients.

Polymorphisms of T helper cell cytokine-associated genes and survival of hemodialysis patients - a prospective study.

BACKGROUND: Circulating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cytokine-associated genes are determinants of mortality in HD patients. METHODS: The study was carried out in 532 prevalent HD subjects who were followed-up for 7 years. HRM analysis was used for IFNL3, IL12A, IL13, and IL4R genotyping. CCL2, IL12B, and IL18 were genotyped using PCR-RFLP analysis. Survival analyses were conducted using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: In univariate analyses, IFNL3 rs8099917 was associated with all-cause mortality in recessive model of inheritance (log-rank test P = 0.044), IL12A rs568408 - in dominant model (log-rank test P = 0.029). Minor homozygotes (the genotype GG) in IFNL3 rs8099917 showed shorter survival during the study (3.6, 1.0-7.0 years vs 4.7, 0.1-7.0 years, P = 0.009) than the major allele (T) bearers. The rs8099917 GG patients demonstrated higher risk of death than the remaining patients (GT + TT) (OR 1.94, 95%CI 1.11-3.40, P = 0.020). Major homozygosity (the genotype GG) in IL12A rs568408 was associated with higher mortality than that shown in bearers of the minor allele (AA + AG) (HR 1.31, 95%CI 1.02-1.69, P = 0.035). In multivariate analyses, however, the mentioned polymorphisms were not independent predictors of survival. CONCLUSIONS: Polymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors.

Self-Reported Physical Activity, Quality of Life, and Psychological Status in Relation to Plasma 25-Hydroxyvitamin D Concentration in Patients Treated with Hemodialysis.

BACKGROUND/AIMS: Vitamin D status is announced among factors that may influence physical performance and mental health. Our aim was to evaluate self-reported physical activity, quality of life, psychiatric functioning, and affects with respect to plasma 25-hydroxyvitamin D [25(OH)D] concentrations in HD patients. METHODS: The study was carried out in HD patients not receiving vitamin D supplements (n = 112). IPAQ-L, QLI-D, GHQ-28, and PANAS were used in psychological evaluations. Plasma 25(OH)D concentration was determined by a chemiluminescent microparticle immunoassay. RESULTS: Plasma 25(OH)D level was suboptimal in all patients (14.6 ± 4.1 ng/ml). Adjusted correlates of 25(OH)D concentration included the GG genotype of GC rs7041 (ß±SE: 1.77± 0.70, P=0.014), female sex (ß±SE: -2.19±0.75, P=0.004), and treatment with high flux HD (ß±SE: 2.59±0.69, P=0.0003). In adjusted analyses, circulating 25(OH)D showed the independent association with total activity related to domestic and gardening domain (ß±SE: 53.2±23.8, P=0.028), and with moderate-intensity activities (ß±SE: 54.9±27.4, P=0.048), but not with any of quality of life, psychiatric functioning, or affects measures. CONCLUSIONS: Vitamin D status is independently positively associated with physical activity in HD patients. Quality of life and mental health do not seem to be associated with circulating 25(OH)D under condition of its suboptimal levels.

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

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.

Monocyte chemoattractant protein-1 gene (MCP-1-2518 A/G) polymorphism and serological markers of hepatitis B virus infection in hemodialysis patients.

BACKGROUND: The role of MCP1-2518 A/G in hepatitis B virus (HBV) infection is controversial. Our aim was to evaluate the frequency distribution of MCP1-2518 A/G (rs1024611) polymorphic variants in hemodialysis (HD) patients without or with type 2 diabetes in relation to serological markers of HBV infection. MATERIAL AND METHODS: HD patients (n=170, 48 with diagnosis of type 2 diabetes), who tested positive for total antibodies to HBV core antigen (anti-HBc), underwent MCP1 genotyping using polymerase chain reaction-restriction fragment length polymorphism assay. Anti-HBc was accompanied by antibodies to HBV surface antigen (anti-HBs) in 127 individuals. In anti-HBc-positive/anti-HBs-negative patients, HBV surface antigen (HBsAg) was shown in 15 patients and isolated anti-HBc were present in 28 patients. The distribution of MCP1 genotypes in anti-HBc-positive patients was compared to that in healthy subjects (n=437) and anti-HBc-negative HD patients (n=754). RESULTS: There were no significant differences (Ptrend >0.05) in distribution of MCP1 genotypes between anti-HBc-positive patients, anti-HBc-negative subjects, and controls, regardless of anti-HBs or diabetic status. The MCP1-2518G allele prevalence was higher in HBsAg-positive/anti-HBs-negative patients defined as HBV carriers compared to MCP1-2518G allele frequency shown in groups composed of HBsAg-negative HD individuals and controls (50% vs. 28%, Ptrend 0.022). CONCLUSIONS: A frequency distribution of MCP1 polymorphic variants is not associated with anti-HBs development in response to HBV infection in HD patients, independent of diabetic status, but the MCP1-2518G allele may predispose to HBsAg persistence (HBV carrier status).

[A positive test QuantiFERON-TB Gold In-Tube in a patient treated with continuous ambulatory peritoneal dialysis]. / Dodatni wynik testu QuniERON-TB Gold In-Tube u chorej leczonej ciagla ambulatoryjna dializa otrzewnowa.

Patients undergoing renal replacement therapy have a higher risk of developing tuberculosis (TBC) in comparison with normal renal function population. The anergy to the tuberculin skin test, the lack of characteristic clinical symptoms of TBC and typical radiographic signs, and high prevalence of extrapulmonary TBC make the diagnosis in dialysis patients difficult and often delay the treatment. In contrast to the active TBC, latent TBC infection (LTBI) is asymptomatic and is not a direct epidemiological problem. However, in patients with end-stage renal disease prepared for renal transplantation, it is an obstacle to qualifying for immunosuppressive therapy. Treatment of LTBI patients with antimycobacterial medication decreases about 90% risk of developing active TB. Therefore, the possibility of a fast and easy identification of LTBI in this group of patients is extremely important. Test QuantiFERON-TB Gold In-Tube (QFT-G) is a new, simple and rapid diagnostic tool in LTBI and active tuberculosis infection (in conjunction with previously used clinical and microbiological methods). This test has been approved and is used in many European countries and in the USA. In a 65-year old patient, treated for 5 years with continuous ambulatory peritoneal dialysis, positive QFT-G results were shownin the course of diagnosis before reporting to the transplant program. After conducting an extensive diagnosis for tuberculosis infection (epidemiological interview, clinical examination, imaging studies, cultures by MB/BacT and the conventional method, consultations with a pulmonologist), latent form of tuberculosis was diagnosed with unspecified location. Due to the positive QFT-G and the need for future immunosuppressive treatment after kidney transplantation, a three-month prophylactic treatment with Rifamazyd 450 mg per day was included. After treatment, the patient entered the waiting list for a kidney transplant. Test QFT-G, in conjunction with other conventional methods is a good and rapid diagnostic tool in the identification of LTBI.

Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection.

Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (anti-HBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre >10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre >10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs >10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0-2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6-24.9, P < 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1-0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03-0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection.

[Gene polymorphism of the vitamin D receptor, vitamin D-binding protein and calcium-sensing receptor in respect of calcium-phosphate disturbances in chronic dialysis patients]. / Polimorfizm genów receptora witaminy D, bialka wiazacego witamine D i receptora wrazliwego na wapn w odniesieniu do zaburzen gospodarki wapniowo-fosforanowej u chorych przewlekle dializowanych.

Dialysed patients suffering from chronic kidney disease (CKD) show varied levels of concentration of parathyroid hormone (PTH) in the blood. One of the factors in charge of regulating levels of PTH concentration is 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. Its deficiency in advanced stages of CKD is common. Vitamin D supplementation is not always effective in reaching levels of PTH concentration recommended by KDIGO for the dialysed patients. That suggests, among other things, disturbances in 1,25-(OH)2D3, reaching its place of target effect and having the desired final result. Disturbances of vitamin D target pathway can be genetically conditioned, hence the aim of this paper is to describe the distribution of polymorphic variants of vitamin D-binding protein gene (VDBP), vitamin D receptor gene (VDR) and gene of the calcium-sensing receptor (CaSR) with respect to PTH concentrations in serum and response to cinacalcet treatment in patients with secondary hyperparathyroidism in view of the differences in demographical, clinical and laboratory data of the dialysed patients.

Associations of ANGPTL6, DOCK6, FABP1, and PCSK9 single-nucleotide variants with hypercholesterolemia in the Polish population: a cross-sectional study.

INTRODUCTION: Hypercholesterolemia is a chronic noncommunicable disease predisposing to cardiovascular diseases. Genome­wide association studies have shown that more than 500 common nucleotide variants are associated with dyslipidemia. OBJECTIVES: We evaluated associations between selected nucleotide variants in ANGPTL6, DOCK6, FABP1, and PCSK9 genes and hypercholesterolemia in the Polish adult population sample. PATIENTS AND METHODS: The study included 109 patients with hypercholesterolemia and 251 individuals with no diagnosed lipid disorder. Genotyping of ANGPTL6 rs8112063, DOCK6 rs737337 and rs17699089, FABP1 rs2241883 and rs2919872, and PCSK9 rs562556 and rs11206510 was carried out using highresolution melting curve analysis. Serum concentrations of FABP1, PCSK9, ANGPTL6, and ANGPTL8 were determined in 51 individuals by enzyme­linked immunosorbent assay. RESULTS: Carriers of the FABP1 rs2919872 CC genotype were over 2.5­fold less likely to be diagnosed with hypercholesterolemia than carriers of the T allele (odds ratio [OR], 0.386; 95% CI, 0.203-0.735; P = 0.003; Pcorr = 0.006). There were no associations between rs2919872 and serum lipid concentrations. Carriers of the ANGPTL6 rs8112063 C allele had an almost 2­fold higher risk of developing hypercholesterolemia than carriers of the T allele (OR, 1.820; 95% CI, 1.053-3.144; P = 0.03; Pcorr = 0.046). Moreover, the carriers of the ANGPTL6 rs8112063 C allele had higher serum concentrations of high-density lipoprotein cholesterol than those with TT genotype (P = 0.009). There were no significant associations between the other tested variants and hypercholesterolemia. CONCLUSIONS: FABP1 rs2919872 and ANGPTL6 rs8112063 are associated with a risk of hypercholesterolemia in the Polish population.

Interleukin-18 promoter polymorphism and development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients.

BACKGROUND: Interleukin (IL)-18 is involved in hepatitis B virus (HBV) clearance and augments antibodies against surface antigen of HBV (anti-HBsAg) production during DNA vaccination. The IL-18 -1297C>T (rs360719) polymorphism may modulate the IL-18 expression. AIM: To determine the potential association of IL-18 -1297C>T polymorphism with development of anti-HBsAg in hemodialysis (HD) patients. METHODS: The frequency of IL-18 -1297C>T alleles and genotypes was identified by polymerase chain reaction restriction fragment length polymorphism in 435 HD patients. Group 1 (n = 219) developed an anti-HBsAg titer >10 IU/l as a result of vaccination or HBV transmission. Group 2 (n = 216) included patients who did not develop an anti-HBsAg titer >10 IU/l in response to at least one full series of vaccination or HBV transmission. The significance of genotype frequency was tested using the Fisher exact test. RESULTS: In group 1, the frequencies of -1297CC, -1297CT and -1297TT genotypes were 7.3, 39.7 and 53.0%, respectively, and in group 2 they were 1.9, 42.1 and 56.0%, respectively. The odds ratio for CC versus CT + TT was 0.239 (95% CI 0.079-0.728, p = 0.010), and for CC versus TT it was 0.240 (95% CI 0.078-0.738, p = 0.009). CONCLUSION: In HD patients, the IL-18 -1297CC genotype may play a role in anti-HBsAg development in response to HBV surface antigen.

Disseminated cutaneous Kaposi sarcoma in a patient receiving triptolide/tripdiolide for rheumatoid arthritis.

BACKGROUND: To date, Kaposi sarcoma has not been mentioned among the adverse effects of triptolide/tripdiolide, ethyl acetate extracts or polyglycosides of the Chinese herbal remedy Tripterygium wilfordii Hook F. CASE REPORT: A patient was diagnosed with rheumatoid arthritis at the age of 29 years. She underwent treatment with corticosteroids, methotrexate and gold sodium thiosulfate, and was chronically taking ketoprofen. At the age of 59 years she started to take a powder (≈2 g/day) from a Chinese physician for treatment of rheumatoid arthritis. This powder was supplied to her regularly for 10 years. At the age of 69 years, multiple soft, violaceous to dark-red patches, plaques, nodules and blisters of varying sizes appeared on a background of severely edematous skin on her legs, and later on her arms. Biopsy specimens of the leg lesions were diagnostic for human herpesvirus 8-associated Kaposi sarcoma. Triptolide (235 µg/1 g) and tripdiolide were found in the Chinese powder by the use of Liquid Chromatography Electrospray Ionization Mass Spectrometry. Administration of the powder was stopped and medication with paclitaxel was introduced. General condition of the patient improved and skin lesions diminished significantly. CONCLUSIONS: This case indicates a possible association between triptolide/tripdiolide chronic intake and development of human herpesvirus 8-associated Kaposi sarcoma. Triptolide/tripdiolide could contribute to development of Kaposi sarcoma by reactivation of latent human herpesvirus 8, permitted by immunosuppression induced by triptolide.

Antibodies to hepatitis B virus surface antigen and interleukin 12 and interleukin 18 gene polymorphisms in hemodialysis patients.

BACKGROUND: The interleukin (IL)18 rs360719 CC genotype is associated with the development of antibodies to hepatitis B virus surface antigen (anti-HBs) in hemodialysis (HD) patients. IL18 shares biological properties with IL12 in promoting the T-hepler 1 (Th1) system. We studied whether polymorphisms in the IL12A 3` untranslated region (UTR) and IL12B 3`UTR may contribute to anti-HBs development (titre ≥ 10 IU/L) in HD patients either individually or jointly with the IL18 polymorphism. METHODS: In 518 HD patients and 240 controls the IL12A rs568408 3'UTR G > A polymorphism was genotyped by high-resolution melting curve analysis. Polymerase chain reaction restriction fragment length polymorphism was used to detect the IL12B rs3212227 3'UTR A > C and IL18 -1297 T > C rs360719 polymorphisms. The associations between the IL12A, IL12B and IL18 genotypes and the risk of impaired anti-HBs development were estimated by computing the odds ratios and their 95% confidence intervals using logistic regression analysis. RESULTS: In the logistic regression analysis, the higher frequency of rs360719 CC individually (2.9% in 207 patients without anti-HBs development vs 8.0% in 311 patients with anti-HBs development, p = 0.009) and of rs360719 CC combined with rs568408 GG (p = 0.048), rs568408 GA (p = 0.035), rs568408 GG/AA (p = 0.034) or rs3212227 AA (p = 0.046) was associated with an increased chance for the development of anti-HBs in HD patients. Patients bearing both rs568408 AA and rs360719 TT had a 10.9-fold or 8.9-fold lower chance, respectively, to develop anti-HBs compared with those carrying any other genotype (p = 0.005) or those who had both wild-type rs568408 GG and rs360719 TT (p = 0.011). Carriers of both rs3212227 CC and rs360719 TC had a 4.6-fold lower chance for anti-HBs development than carriers of any other genotype (p = 0.042). CONCLUSION: Development of anti-HBs in HD patients is associated with gene polymorphisms of interleukins involved in the Th1 system.

[Calcimimetic drugs in stage 3-5 chronic kidney disease]. / Leki kalcymimetyczne w stadium 3-5 przewleklej choroby nerek.

This review is focused on results of application of calcimimetic drug--cinacalcet in the treatment of secondary hyperparathyroidism in patients in 3-5 stage chronic kidney disease (CKD), excluding dialysis patients (stage 5D CKD). Oral administration of cinacalcet (15-180 mg/day) significantly reduced plasma parathormone (PTH) concentrations (> or = 30% as compared to the baseline values), but simultaneously side effects occurred, among them hypocalcemia and hyperphosphatemia. Hypocalcemia was a reason for cinacalcet withdrawal in 2-15% of patients. There is a lack of studies showing the influence of advantages and disadvantages of long-term administration of cinacalcet on outcome of 3-5 stage CKD patients.

[Dilatation of the left atrium as one of the indicators of worse prognosis in patients treated with intermittent hemodialysis]. / Powiekszenie lewego przedsionka jako jeden ze wskazników gorszego rokowania u chorych leczonych powtarzana hemodializa.

UNLABELLED: Cardiovascular diseases are the most frequent cause of death in patients undergoing treatment with hemodialysis (HD). Echocardiography is the established method in diagnosis and searching for HD patients with an increased risk of death from cardiovascular events. The aim of the study was to show parameters, obtained also in the echocardiographic examination, which are helpful to distinguish persons with the worse prognosis among the group of HD patients. MATERIAL AND METHODS: Observation was done in 56 patients. Echocardiographic examination was performed at baseline before and after HD. The observation lasted 26.3 +/- 13.6 months. The analysis included the effect of the patient demographic characteristics, clinical and echocardiographic parameters: gender, age, duration of renal replacement therapy, body mass index, presence of ischemic heart disease, chronic heart failure, presence of valvular defects, hypertension, pharmacological therapy, systolic and diastolic left ventricular function, the size of the left and right atrium, atrial volume changes that occur due to decreased blood volume during HD treatment on the death risk. RESULTS: In the group of 56 patients significantly worse survival was shown in persons with symptoms of cardiac failure. After 3 years of the observational study in the group without diagnosis of chronic cardiac failure 90.9% patients survived, whereas in the group with diagnosis of cardiac failure 51.0% (p = 0.020). In the group of patients with diagnosis of severe valvular disease 14.3% survived, whereas in the group without severe valvular disease 66.1% survived, (p = 0.009). Among patients without diagnosis of arterial hypertension 30.0% survived; in the group with diagnosis of arterial hypertension 65.9% (p = 0.016). In the group of patients with left atrial dimension > 50 mm all patients died, whereas in the group of patients with left atrial dimension < or = 50 mm 62.6% (p = 0.010) survived. CONCLUSIONS: HD patients with worse survival prognosis can be identified by echocardiographic examination showing risk factors which were severe valvular disease and dilatation of the left atrium.