DNMT1, DNMT3A and DNMT3B gene variants in relation to ovarian cancer risk in the Polish population

Studies have demonstrated that changes in DNA methylation of cancer related genes can be an elementary process accounting for ovarian tumorigenesis. Therefore, we evaluated the possible association of single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) genes, including DNMT1, DNMT3B, and DNMT3A, with ovarian cancer development in the Polish population. Using PCR–RFLP and HRM analyses, we studied the prevalence of the DNMT1 rs8101626, rs2228611 and rs759920, DNMT3A rs2289195, 7590760, rs13401241, rs749131 and rs1550117, and DNMT3B rs1569686, rs2424913 and rs2424932 SNPs in patients with ovarian cancer (n = 159) and controls (n = 180). The lowest p values of the trend test were observed for the DNMT1 rs2228611 and rs759920 SNPs in patients with ovarian cancer (p _trend = 0.0118 and p _trend = 0.0173, respectively). Moreover, we observed, in the recessive inheritance model, that the DNMT1 rs2228611 and rs759920 SNPs are associated with an increased risk of ovarian cancer development [OR 1.836 (1.143–2.949), p = 0.0114, p _corr = 0.0342, and OR 1.932 (1.185–3.152), p = 0.0078, p _cor=0.0234, respectively]. However, none of other nine studied SNPs displayed significant contribution to the development of ovarian cancer. Furthermore, haplotype and multifactor dimensionality reduction analysis of the studied DNMT1, DNMT3B, and DNMT3A polymorphisms did not reveal either SNP combinations or gene interactions to be associated with the risk of ovarian cancer development. Our results may suggest that DNMT1 variants may be risk factors of ovarian cancer.     

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.     

Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a polish population

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital anomalies, with a complex and still not fully understood etiology. Given the important role of the Wnt/β‐catenin pathway during craniofacial development, we decided to test the hypothesis that common polymorphic variants of the genes encoding crucial components of this signaling pathway might contribute to the risk of NSCL/P in the Polish population. METHODS: A set of 19 single nucleotide polymorphisms (SNPs) in the APC, AXIN1, AXIN2, CTNNB1, DVL2, and GSK‐3β genes were analyzed using restriction fragment length polymorphism and high‐resolution melting curve methods in a group of 280 patients with NSCL/P and a properly matched control group (n = 330). RESULTS: Both single‐marker and haplotype analyses showed an association between SNPs in the DVL2 gene and the risk for NSCL/P. The strongest association was found under an overdominant model for the rs35594616 variant located in the exonic sequence of DVL2 (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.37–2.62; p < 0.0001). Moreover, the gene‐gene interaction analysis revealed a significant epistatic interaction between DVL2 gene SNPs in the susceptibility to orofacial clefts. Borderline association with a decreased risk of NSCL/P was also observed for the AXIN2 rs3923087 variant (dominant model OR, 0.69; 95% CI, 0.50–0.95; p = 0.03). CONCLUSION: This study suggests that polymorphic variants of the Wnt/β‐catenin pathway genes have a role in the susceptibility to orofacial clefts. The DVL2 and AXIN2 genes might be candidate genes for this craniofacial anomaly in the Polish population. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Copepod Population-Specific Response to a Toxic Diatom Diet

Diatoms are key phytoplankton organisms and one of the main primary producers in aquatic ecosystems. However, many diatom species produce a series of secondary metabolites, collectively termed oxylipins, that disrupt development in the offspring of grazers, such as copepods, that feed on these unicellular algae. We hypothesized that different populations of copepods may deal differently with the same oxylipin-producing diatom diet. Here we provide comparative studies of expression level analyses of selected genes of interest for three Calanus helgolandicus populations (North Sea, Atlantic Ocean and Mediterranean Sea) exposed to the same strain of the oxylipin-producing diatom Skeletonema marinoi using as control algae the flagellate Rhodomonas baltica. Expression levels of detoxification enzymes and stress proteins (e.g. glutathione S-transferase, glutathione synthase, superoxide dismutase, catalase, aldehyde dehydrogenases and heat shock proteins) and proteins involved in apoptosis regulation and cell cycle progression were analyzed in copepods after both 24 and 48 hours of feeding on the diatom or on a control diet. Strong differences occurred among copepod populations, with the Mediterranean population of C. helgolandicus being more susceptible to the toxic diet compared to the others. This study opens new perspectives for understanding copepod population-specific responses to diatom toxins and may help in underpinning the cellular mechanisms underlying copepod toxicity during diatom blooms.     

The role of environmental factors in the induction of oxidative stress in zebra mussel (<Emphasis Type="Italic">Dreissena polymorpha</Emphasis>)

The aim of this study was to investigate the influence of specific environmental factors, such as temperature, pH, oxygen concentration, and phosphate, nitrate, chloride, sodium, potassium, sulphate, magnesium and calcium ions concentration, as well as microcystins, on the seasonal variations in the activity of the antioxidant system of the zebra mussel. We examined changes in lipid peroxidation (LPO) levels, glutathione content and the catalase activity of mussels inhabiting the two ecosystems, which differ due to their trophic structure and the presence of toxic cyanobacteria. The results show a relationship between the activity of the antioxidant system of zebra mussels and the seasonal fluctuations of environmental parameters: the symptoms of oxidative stress were generally the highest during spring and the lowest during summer in both ecosystems. Our study also revealed that regardless of the study area the most important factors determining the activity of the antioxidant defences of mussels were the mineral composition (particularly magnesium and calcium ions concentrations) and physical parameters of the water (oxygen concentration and pH). However, factors resulting from the trophic status of studied ecosystems, such as limitations in food resources or high concentration of microcystins during cyanobacterial blooms, were periodically responsible for increased level of LPO in the tissues of zebra mussel. These findings may indicate a limited tolerance of the zebra mussel to the local environmental conditions.