IL-1ß, IL-10 and TNF-α polymorphisms may affect systemic lupus erythematosus risk and phenotype.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease, and IL-1ß, IL-10, and TNF-α genes are important in the pathogenesis of this disease. We studied the impact of IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, TNF-α -308, TNF-α -238, and TNF-α +489 polymorphisms on SLE risk and phenotype in SLE patients and healthy controls. METHODS: We genotyped SLE patients and healthy controls by real-time PCR on QuantStudio 5 (Applied Biosystems) and measured levels of cytokines by enzyme-linked immunosorbent assay (ELISA). RESULTS: We indicated that TNF-α -308, IL-10 -592, IL-10 -1082, IL-1ß-511 and IL-1ß +3953 polymorphisms affect SLE risk. Furthermore, we exposed that some of the TNF-α +489, TNF-α -238, IL-10 -1082 and IL-1ß +3953 genotypes are connected with the SLE phenotype. Moreover, we discovered the linking between specific genotypes and the serum concentrations of TNF-α, IL-1ß, and IL-10. CONCLUSIONS: In conclusion, our study revealed that IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, and TNF-α -308 polymorphisms may affect SLE risk and phenotype.

Long noncoding RNA CCAT1 rs67085638 SNP contribution to the progression of gastric cancer in a Polish population.

The role of the long noncoding RNA CCAT1 NC_000008.10:g.128220661C > T (rs67085638) in the development of colon cancer has been reported. Therefore, we assessed the prevalence of rs67085638 in patients with gastric cancer (GC). We also evaluated the effect of rs67085638 on B-cell-specific Moloney leukaemia virus insertion site 1 (BMI1) transcripts in primary GC and counterpart histopathologically confirmed disease-free margin tissue. Using high-resolution melting analysis, we evaluated rs67085638 frequency in patients with the GC genotype (n = 214) and controls (n = 502) in a Polish Caucasian population. qRT-PCR was used to determine BMI1 transcripts. We observed the trend of rs67085638 association in all patients with GC (ptrend = 0.028), a strong risk of the GC genotype in male (ptrend = 0.035) but not female (ptrend = 0.747) patients, and the association with non-cardia GC (ptrend = 0.041), tumour stages T3 (ptrend = 0.014) and T4 (ptrend = 0.032), differentiation grading G3 (ptrend = 0.009), lymph node metastasis stage N3 (ptrend = 0.0005) and metastasis stage M0 (ptrend = 0.027). We found that significantly increased BMI1 transcripts were associated with the primary GC genotype classified as grade G3 (p = 0.011) and as lymph node metastasis N3 (p = 0.010) and counterpart marginal tissues (p = 0.026, p = 0.040, respectively) from carriers of the T/T versus C/C genotypes. rs67085638 may contribute to increased BMI1 transcripts and the progression and rapid growth of GC.

The Role of MECP2 and CCR5 Polymorphisms on the Development and Course of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease. SLE is described by production of autoantibodies and causes damage of many organs. T-cells play a crucial role in SLE pathogenesis. T-cells intensify inflammation through a number of processes, which leads to autoimmunization. CCR5 and MECP2 genes are linked with T-cells and pathogenesis of SLE. Polymorphisms in these genes are related with the prognostic factors of risk of disease onset and disease severity. The aim of this study was to estimate the influence of polymorphisms in MECP2 and CCR5 genes on the development and course of systemic lupus erythematosus. We examined 137 SLE patients and 604 healthy controls. We studied polymorphisms for CCR5 gene: rs333 and for MECP2: rs2075596, rs1734787, rs17435, and rs2239464. We genotyped our MECP2 samples and we performed a restriction fragment length polymorphism (RFLP) analysis for CCR5 samples. We showed a risk factor for allele T in rs17435 and for allele A in rs2075596 in MECP2. We noticed that MECP2 rs2075596 G/A, rs1734787 C/A, rs17435 A/T, and rs2239464 G/A polymorphisms are more prevalent in SLE patients than in healthy controls. We believe that above-mentioned MECP2 polymorphisms can be considered as SLE susceptibility factor.

IL-6 and TGF-ß gene polymorphisms, their serum levels, as well as HLA profile, in patients with systemic lupus erythematosus.

OBJECTIVES: The aim of the study was to explore whether TGF-ß and IL-6 gene polymorphisms may be associated with SLE and assess the frequency of HLA-DRB1 alleles in Polish systemic lupus erythematosus (SLE) patients. METHODS: 216 SLE patients and 552 healthy individuals were examined for TGF-ß rs1800469 and rs1800470 by TaqMan SNP genotyping assay and for and IL-6(rs2069827 and rs1800795 using the PCR- RFLP method. RESULTS: An increased frequency of TT genotype and T allele of the TGF ß -509 C/T was found in SLE patients (p=0.02). The TGF-ß 869 C allele was more frequent in SLE patients. The genotype-phenotype analysis showed association between the TGF ß -509 C/T and mean value of CRP, ESR, haemoglobin, APTT, Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the TGF- ß 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-ß and IL-6 serum level were found in SLE patients compared to controls (both p<0.0001). In SLE patients with the TGF-ß -509 TT genotype have shown positive association with the TGF-ß serum levels. Polish SLE patients have strong positive association with HLA-DRB1*52.1, and negative with the HLA-DRB1*07:01 allele. HLA-DRB1*52.1 was also associated with higher TGF-ß serum levels in the Polish population. CONCLUSIONS: Our results suggested that the TGF ß -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.

The association of CCAT2 rs6983267 SNP with MYC expression and progression of uterine cervical cancer in the Polish population.

PURPOSE: Previous studies have reported a significant contribution of NC_000008.10:g.128413305 G>T (rs6983267) single-nucleotide polymorphism (SNP) in the MYC enhancer region to the susceptibility of various cancers. However, the role of rs6983267 SNP in cervical cancer (CC) development and progression has not been demonstrated to date. Therefore, we evaluated the role of rs6983267 SNP in MYC expression in cervical cancers and non-cancerous cervical tissues. In addition, we assessed the role of this SNP in the development and progression of CC. METHODS: Using high-resolution melting analysis, we evaluated rs6983267 SNP frequency in women diagnosed with cervical squamous cell carcinoma (SCC) (n = 481) and controls (n = 502) in a Polish Caucasian population. Logistic regression analysis was employed to adjust for the effects of age, parity, oral contraceptive use, tobacco smoking, and menopausal status. RESULTS: Dividing patients based on clinical characteristics demonstrated an association of the rs6983267 genotype with tumor stage III and grade of differentiation G2 and G3. The p trend value calculated for the rs6983267 SNP in patients with stage III was 0.0006. We also observed a significant contribution of rs6983267 SNP to tumor grade of differentiation G2 and G3. Additional contributors were oral contraceptive use, smoking, and postmenopausal age. We found statistically significant increase of MYC transcript levels in cervical SCC tissues from carriers of the GG vs. T/T (p < 0.00001), G/T vs. T/T (p = 0.0002), and in the non-cancerous cervical tissues from carriers of the GG vs. T/T (p = 0.00046). CONCLUSION: The rs6983267 SNP may contribute to the increased MYC expression as well as the spread and rapid growth of cervical SCC as compared to lower grade carcinomas.

Neurologic complications in kidney transplant recipients.

Transplantology experiences continuous growth and kidney transplantation is the most frequently transplanted solid organ. Metabolic, cardiovascular, infectious or kidney function-related aspects are widely recognised and are of key interest for transplant doctors. Neurological complications seen in these patients, although known, are less covered in the literature. According to some reports, neurologic symptoms are experienced by almost 9 per 10 transplant recipients. The intensity, severity and type of abnormalities may vary, and most frequently the complications seem to be associated with a direct or indirect effect of immunosuppressive medications, including their direct effect on cells, on blood vessels, and susceptibility to infections. Increasing age of transplant recipients and relaxation of transplantation eligibility criteria enriches the population with patients already compromised, with a higher present risk of stroke, neuropathy, malignancy etc. Research on and introduction to clinical practice of new agents like belatacept, proteasome inhibitors, or modified release formulations of tacrolimus, changes the picture and type of abnormalities within the nervous or neuromuscular system but does not eliminate them. Thus, it seems justified to remind the society of the whole array of neurologic complications they can see in their practice despite advances in the field..

Analysis of rs8067378 Polymorphism in the Risk of Uterine Cervical Cancer from a Polish Population and its Impact on Gasdermin B Expression.

OBJECTIVE: We studied the role of the NC_000017.10:g.38051348A>G (rs8067378) single nucleotide polymorphism (SNP) located 9.5 kb downstream of gasdermin B (GSDMB), in the development and progression of cervical squamous cell carcinomas (SCC). METHODS: Using high-resolution melting curve analysis, we genotyped this SNP in patients with cervical SCC (n = 486) and controls (n = 511) from the Polish Caucasian population. Logistic regression analysis was used to adjust for the effect of confounders such as age, parity, oral contraceptive use, tobacco smoking, and menopausal status. The effect of this SNP on the expression of GSDMB was studied by reverse transcription and quantitative real-time polymerase chain reaction analysis of GSDMB transcript levels in SCC tissues. RESULTS: For all patients with SCC, the p trend value calculated for rs8067378 was statistically significant (p trend = 0.0019). The adjusted odds ratio for the G/G vs. A/A genotype was 1.304 (95% confidence interval 1.080-1.574, p = 0.0057) and the adjusted odds ratio for the G/A + G/G vs. A/A genotype was 1.444 (95% confidence interval 1.064-1.959, p = 0.0181). We also found a significant association of the rs8067378 SNP with tumor stages III, IV, and grade of differentiation G3, and with parity, oral contraceptive use, smoking, and women of postmenopausal age. We found increased GSDMB1 isoform transcripts in the cancerous and non-cancerous tissues from carriers of the G allele vs. carriers of the A/A genotype. CONCLUSIONS: The rs8067378 SNP variants may increase the expression of GSDMB and the risk of the development and progression of cervical SCC.

17ß-hydroxysteroid dehydrogenase type Gene 1937 A > G Polymorphism as a Risk Factor for Cervical Cancer Progression in the Polish Population.

The role of 17ß-estradiol (E2) in the development of cervical tumor (CT) has been demonstrated. 17ß Hydroxysteroid dehydrogenase type 1 (HSD17B1) converts estrone (E1) into E2. We aimed to study the distribution of the HSD17B1937 A > G (rs605059) single nucleotide polymorphism (SNP) in women (n = 383) with CT and controls (n = 401) from the Polish population. The p-trend value evaluated for HSD17B1 rs605059 was 0.0233 for all patients. The A/A vs G/G genotype significantly contributed to all patients with CT, and the Odds Ratio (OR) was 1.570 (95 % CI = 1.053-2.343; p = 0.0266). Stratification of the patients based on tumor stage and histological grade indicated the contribution of HSD17B1937 A > G to stages III and IV. The p-value was 0.0010. The OR for the A/A vs G/G genotype was 2.992 (95 % CI = 1.627-5.502, p = 0.0003), the OR for the A/G vs G/G genotype was 2.545 (95 % CI = 1.410-4.593, p = 0.0015) and the OR for the A/A and A/G vs G/G genotype was 2.724 (95 % CI = 1.546-4.799, p = 0.0004). Moreover, we observed a contribution of the rs605059 SNP to histological grade G3 status. The p-value was 0.0042. The OR for the A/A vs G/G genotype was 5.632 (95 % CI = 1.644-19.290, p = 0.0026), the OR for the A/G vs G/G genotype was 4.213 (95 % CI = 1.244-14.265, p = 0.0113) and the OR for the A/A and A/G vs G/G genotype was 4.780 (95 % CI = 1.456-15.687, p = 0.0033). Our study indicated that the HSD17B1937 A > G transition is a risk factor for CT, especially for stages III and IV and histological grade G3.

Involvement of myeloperoxidase gene polymorphism 463G>A in development of cervical squamous cell carcinoma.

BACKGROUND: The myeloperoxidase (MPO) -463G>A (rs2333227) polymorphism has been linked with increased susceptibility to the development of various malignancies. However, the data on the association of the MPO -463G>A transition with cervical cancer remain inconsistent. METHODS: Using high resolution melting analysis we genotyped this polymorphism in women with cervical squamous cell carcinoma (SCC) (n = 476) and controls (n = 493) from a Polish Caucasian population. Logistic regression analysis was used to adjust for the effect of confounders such as age, parity, oral contraceptive use, tobacco smoking, and menopausal status, and revealed that the MPO -463G>A single nucleotide polymorphism (SNP) was associated with an increased risk of SCC. RESULTS: The adjusted odds ratio (OR) for patients with the A/A genotype versus G/G genotype was 0.718 (95% CI 0.531-0.972, p = 0.0316). Stratified analyses between the MPO -463G>A polymorphism and SCC risks demonstrated a protective role of the MPO -463G>A SNP in patients with a positive history of parity and negative history of tobacco smoking. In patients with a positive history of parity, the age-adjusted OR for the A/A versus G/G genotype was 0.667 (95% CI 0.479-0.929, p = 0.0164). The age-adjusted OR for patients with a negative history of tobacco smoking for the A/A versus G/G genotype was 0.491 (95% CI 0.313-0.770, p = 0.0019). CONCLUSIONS: Our study demonstrated that the MPO -463G>A SNP may protect from SCC in women from Polish Caucasian populations.