Deiodinases, Organic Anion Transporter Polypeptide Polymorphisms, and Thyroid Hormones in Patients with Myocardial Infarction

Aim: To investigate the association among deiodinases (DIO), organic anion-Transporting polypeptide 1C1 (OATP1C1) gene polymorphisms, and thyroid hormones (THs) in patients with acute myocardial infarction (AMI). Methods: In summary, 290 patients with AMI were evaluated for sociodemographic and clinical characteristics, coronary artery disease (CAD) risk factors, and comorbidities, as well as circulating thyroid-stimulating hormone and TH (triiodothyronine [T3], thyroxine [T4], free T3, free T4, and reverse T3) levels. Ten single nucleotide polymorphisms for thyroid axis related genes: DIO1 (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), DIO2 (rs225014-T/C, rs225015-G/A), DIO3 (rs945006-T/G), and OATP1C1 (rs10444412-T/C, rs10770704-C/T, rs1515777-A/G, rs974453-G/A) were genotyped. Results: Marginal associations were observed between the DIO1, DIO2, and OATP1C1 gene polymorphisms and almost all analyzed THs (p's < 0.05). After controlling for potential confounders, the OATP1C1 rs1515777-A/G minor allele homozygous genotype (G/G) was associated with a decrease in circulating free T3 and free T3/free T4. In the AMI cohort, associations between: DIO1 rs12095080 and hypertension; DIO2 rs225015 and diabetes mellitus; and the OATP1C1 rs974453 genotype, and AMI type were established. Conclusions: DIO1 and DIO2 gene polymorphisms are mainly associated with T3, free T4, free T3/free T4, and [natural-log transformed (ln)] reverse T3 levels, while the OATP1C1 minor allele homozygous genotype is associated with free T3 and free T3/free T4 in CAD patients after AMI

<it>MGMT</it>, <it>GATA6</it>, <it>CD81</it>, <it>DR4</it>, and <it>CASP8</it> gene promoter methylation in glioblastoma

<p>Abstract</p> <p>Background</p> <p>Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome.</p> <p>Methods</p> <p>The methylation status of <it>MGMT</it>, <it>CD81</it>, <it>GATA6</it>, <it>DR4</it>, and <it>CASP8</it> in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis.</p> <p>Results</p> <p>The overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: <it>MGMT</it> in 51.3%, <it>GATA6</it> in 68.4%, <it>CD81</it> in 46.1%, <it>DR4</it> in 41.3% and <it>CASP8</it> in 56.8% of tumors. Methylation of <it>MGMT</it> was associated with younger patient age (p < 0.05), while <it>CASP8</it> with older (p < 0.01). <it>MGMT</it> methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of <it>CASP8</it> was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> as independent predictors for glioblastoma patient outcome (p < 0.05). <it>MGMT</it> and <it>GATA6</it> were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy.</p> <p>Conclusions</p> <p>High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> genes methylation in glioblastoma patient outcome.</p