Anna Sowińska

IL4R and IL13 polymorphic variants and development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to HBV vaccination or infection

We searched for an association between the interleukin 4 receptor gene (IL4R) rs1805015 and interleukin 13 gene (IL13) rs20541 polymorphisms and the development of antibodies to hepatitis B surface antigen (anti-HBs) in the case of hepatitis B virus (HBV) vaccination or infection in hemodialysis (HD) patients. HD patients who failed to respond to HBV vaccination did not differ in genotype frequencies of IL4R (TT 72.7%, CT 22.6%, CC 4.7%) and IL13 (CC 59.0%, CT 34.2%, TT 6.8%) from vaccine responders (IL4R TT 68.0%, CT 27.3%, CC 4.7%; IL13 CC 55.0%, CT 38.5%, TT 6.5%). HD patients who did not develop anti-HBs despite HBV infection also did not differ in genotype frequencies of IL4R (TT 67.8%, CT 26.8%, CC 5.4%) and IL13 (CC 60.7%, CT 33.9%, TT 5.4%) from HD patients who developed an anti-HBs response (IL4R TT 65.4%, CT 30.8%, CC 3.8%; IL13 CC 60.5%, CT 34.6%, TT 4.9%). In HD patients, neither the IL4R nor IL13 polymorphism is associated with anti-HBs development irrespective of whether an immunization is provoked by HBV vaccination or HBV infection.

Single nucleotide polymorphisms of vitamin D binding protein, vitamin D receptor and retinoid X receptor alpha genes and response to hepatitis B vaccination in renal replacement therapy patients.

Aim: Vitamin D (VD) was recently associated with response to hepatitis B vaccination in chronic kidney disease. We investigated whether polymorphisms in VD binding protein (GC), VD receptor (VDR) and retinoid X receptor α (RXRA) genes were associated with response to hepatitis B vaccination in renal replacement therapy (RRT) patients. Method: The study was carried out on 692 responders and 223 non-responders. Results: After adjustment for gender, age at the RRT onset, RRT vintage, chronic glomerulonephritis as a cause of renal failure and mean serum parathyroid hormone level, VDR rs1544410 polymorphism was the only one significantly associated with response to hepatitis B vaccination: homozygotes AA (adjusted OR 1.50, 95% CI: 1.17–1.94, p = 0.002) had higher risk to be non-responders than GG homozygotes. Discussion: The VDR rs1544410 AA genotype may play a negative role (but not as an independent factor) in determining response to hepatitis B vaccination in RRT patients.

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/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).

TNF-308 G/A polymorphism and risk of systemic lupus erythematosus in the Polish population

Abstract Objectives. Numerous studies have been performed with TNF-α-308 G/A (rs1800629) single nuclear polymorphism (SNP) to evaluate the risk of SLE in various ethnicities. However, the significance of TNF-α-308 G/A in both clinical and laboratory studies of the disease remains unclear. Methods. Using a high-resolution melting curve analysis, we assessed the prevalence of TNF-α-308 G/A SNP in SLE patients (n = 262) and controls (n = 528) in a Polish population. We also assessed the contribution of this SNP to various clinical symptoms and the presence of autoantibodies in SLE patients. Results. The p-value obtained using a χ2 test for the trend of TNF-α-308 G/A was statistically significant (ptrend = 0.0297). However, using logistic regression analysis for the presence of the HLA-DRB1*03:01 haplotype, we observed that the TNF-α-308 G/A SNP may be the DRB1*03:01-dependent risk factor of SLE in the Polish population. There was a significant contribution of TNF-α-308 A/A and A/G genotypes to arthritis OR = [2.692 (1.503–4.822, p = 0.0007, pcorr = 0.0119)] as well as renal SLE manifestation OR = [2.632 (1.575–4.397, p = 0.0002, pcorr = 0.0034)]. There was a significant association between TNF-α-308 A/A and A/G genotypes and the presence of anti-Ro antibodies (Ab) OR = 3.375(1.711–6.658, p = 0.0003, pcorr = 0.0051). However, the logistic regression analysis revealed that only renal manifestations and the presence of anti-anti-Ro antibodies remained significant after adjustment to the presence of the HLA-DRB1*03:01 haplotype. Conclusion. Our studies indicate that the TNF-α-308 G/A polymorphism may be a DRB1*03:01 haplotype-dependent genetic risk factor for SLE. However, this SNP was independently associated with renal manifestations and production of anti-Ro Ab.

IL-12B Gene Polymorphisms and IL-12 p70 serum levels among patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL‐12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL‐12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty‐four Caucasian RA patients and 341 healthy matched controls were studied using PCR‐RFLP method and high‐resolution melting analysis. Concentration of IL‐12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL‐12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL‐12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL‐12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL‐12p40 + 1188A/C polymorphism as well as IL‐12p70 protein levels may be associated with RA in the Polish population.

Genetic Variants in IL‐12B and IL‐27 in the Polish Patients with Systemic Lupus Erythematosus

To investigate the potential association between IL‐12B and IL‐27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case–control study based on the Polish population. Patients with SLE and healthy individuals were examined for −6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL‐12B and −924A/G (rs153109) and 4730T/C (rs181206) in IL‐27 gene polymorphisms using the high‐resolution melting method, PCR–RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL‐12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL‐12B rs3212227 and IL‐27 rs153109 and rs181206 variants between patients with SLE and controls. IL‐27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL‐12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL‐12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL‐12B rs17860508 and IL‐27 haplotype CG are genetic risk factors for SLE and that both IL‐12B rs17860508 and rs3212227 predict disease phenotype.

Relationship between adipokines and lipid profile in postmenopausal women with different apolipoprotein E genotypes.

ABSTRACT The aim of the authors of this study was to clarify the relationships among apolipoprotein E (ApoE) genotype, blood pressure, lipid profile, serum leptin, and adiponectin in healthy postmenopausal women. The study was conducted between March 2011 and December 2012 on 266 participants aged 50–65 years from the Institute of Rural Health in Lublin, Poland. Results showed that women had four combinations of genotypes: ɛ2/ɛ3, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4. Carriers of different genotypes did not differ in terms of age, body mass index (BMI), blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, and adiponectin levels. Mean low-density lipoprotein (LDL) cholesterol levels were higher in ε4 carriers compared to non-carriers. Fasting serum leptin concentrations were higher in homozygotes ɛ4/ɛ4. Leptin correlated positively with BMI in all study groups and with LDL in ɛ2/ɛ3, ɛ3/ɛ3, and ɛ3/ɛ4. Adiponectin correlated negatively with triglycerides in ɛ2/ɛ3, ɛ3/ɛ3, and ɛ3/ɛ4 and positively with HDL in ɛ2/ɛ3 carriers. Adipokines were not associated with blood pressure. Multiple regression analyses demonstrated associations among leptin, ApoE ɛ4/ɛ4, BMI, and LDL, and among adiponectin, BMI, and triglycerides. In healthy postmenopausal women ɛ4/ɛ4 genotype was associated with lower leptin levels. Homozygosity ɛ4/ɛ4 was associated with a more atherogenic lipid profile and possibly dysregulation of leptin and adiponectin signaling in lipid metabolism.

FLT-1 gene polymorphisms and protein expression profile in rheumatoid arthritis

Objectives Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the FLT-1 polymorphisms with different “angiogenic diseases” suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA. Methods The FLT-1 gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated. Results The FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D’ = 0.97 and r2 = 0.83. The FLT-1 rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls. Conclusion FLT-1 rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.

Role of rs13117307 single nuclear polymorphism in the risk of uterine cervical cancer from Polish population and its impact on exocyst complex component 1 expression

We evaluated the role of NM_001024924.1:c.1330+1646C>T (rs13117307) single nucleotide polymorphism (SNP), situated in the intronic region of exocyst complex component 1 (EXCO1), in the development and spreading of cervical squamous cell carcinoma (SCC). Utilizing high resolution melting curve analysis, we analyzed this polymorphism in patients with cervical SCC (n=485) and controls (n=509) in the Polish Caucasian population. Logistic regression analysis was used to adjust for age, parity, oral contraceptive use, tobacco smoking, and menopausal status. The influence of this polymorphism on the expression of EXCO1 was assessed by reverse transcription and real-time quantitative PCR analysis. For all patients with SCC, the p trend value calculated for rs13117307 was statistically significant (ptrend=0.0158). The adjusted odds ratio (OR) for T/T vs. C/C was 1.434 (95 % CI 1.105-1.861, p=0.007). We also found a significant contribution of rs13117307 to tumor stages III, IV and grade of differentiation G3. Other contributors are parity, oral contraceptive use, smoking, and women of postmenopausal age. We observed significant upregulation of EXCO1 transcript levels in the non-cancerous cervical tissues in carriers of the T/T vs. C/C (p=0.016), as well as an increase in the EXCO1 transcript levels in the cervical SCC tissue in carriers of the T/T vs. C/C (p=0.029) and for T/T vs C/T (p=0.0032). The rs13117307 SNP variants may upregulate the transcription of EXCO1, as well as the risk of development and spreading of cervical SCC.

The Effect of VASER Abdominal Liposuction on Metabolic Profile in Overweight Males

The aim of the current study was to examine the liposuction-induced metabolic changes with regard to release of major adipokines and insulin sensitivity in overweight male patients. Seventeen overweight male patients aged 37.15 ± 9.60 years (6 with diabetes type 2, 11 without comorbidities) and 10 age-matched healthy lean controls were enrolled in the study. Using Vibration Amplification of Sound Energy at Resonance System, ultrasound assisted liposuction was applied onto the deep layers of abdominal subcutaneous adipose tissue. The mean volume supranatant fat was 2208 ± 562 ml. To eliminate the confounding effects of postsurgical inflammation and to evaluate delayed metabolic effects, fasting blood was collected on the day of liposuction, within 1 to 2 months and more than 6 months after surgery. Serum leptin, soluble receptor for leptin, adiponectin, insulin, and glucose concentrations were tested and insulin sensitivity was calculated using updated model Homeostasis Model Assessment 2. Both treatment groups (diabetic and nondiabetic patients) experienced similar postsurgical weight reduction with concomitant lowering of body mass index value at 1 to 2 months follow-up, which was sustained after 6 months from surgery. Improvement in insulin sensitivity at 1 to 2 months follow-up was observed (p = .017 and p = .002, for diabetics and nondiabetics, respectively) and this change persisted over the next 4 months. At the same time, no significant changes in adipokines and soluble leptin receptor were found. These data demonstrate that in terms of metabolic consequences, Vibration Amplification of Sound Energy at Resonance abdominal liposuction might have beneficial effects in overweight diabetic and nondiabetic males by improving their insulin sensitivity.