Younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature atherosclerosis.

BACKGROUND: Premature coronary artery disease is one of the most pressing global issues in modern cardiology. The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients aged < 50 years with myocardial infarction (MI) compared to that in patients aged ≥50 years with MI and to that in young people without MI (no-MI < 50). METHODS: The studied group (MI < 50) consisted of 240 patients aged 26-49 years with MI. The control groups consisted of 240 patients (MI ≥ 50) with MI aged 50-92 years and 240 healthy people aged 30-49 years without a history of MI (no-MI < 50). RESULTS: There were statistically significant differences between the MI < 50 and MI ≥ 50 and no-MI < 50 groups regarding the family history of premature MI/ischaemic stroke and the percentage of patients with ≥2 relatives affected (10.8, 2.9, and 3.7%, respectively; p < 0.0001). There was a statistically significant difference in the patient age at the first MI occurrence among patients without a family history of premature CVD, those with 1 affected relative, and those with ≥2 affected first-degree relatives (56.6, 48.6 and 41.8 years, respectively) as well as those with affected first- and second-degree relatives (56.5, 50.7 and 47.0 years, respectively). CONCLUSIONS: A younger age of patients with myocardial infarction is associated with a higher number of relatives with a history of premature MI/ischaemic stroke. Thus, the family history of premature atherosclerosis involving not only first- but also second-degree relatives seems to be a valuable factor in CVD risk evaluation in young people.

ESR2 gene G1730A variant is associated with triglycerides level and myocardial infarction in young men but not in women.

OBJECTIVES: The aim of the study was to investigate the role of estrogen receptor type 2 gene (ESR2) variant G1730A in myocardial infarction (MI) in young age. METHODS: Genotyping was performed with restriction fragments length polymorphism method in 158 patients (79.1% men) with MI aged <50 years (studied group) and in control groups: 150 healthy individuals aged <50 years (63.3% men) and 202 patients (64.3% men) with MI aged ≥50 years. RESULTS: The AA genotype of ESR2 G1730A variant was significantly more frequent in men with MI aged <50 comparing to men with MI aged ≥50 (21.6% vs. 8.4%, P = 0.004) and to healthy young men (21.6% vs. 11.6%, P = 0.048). There was statistically significant difference between AA genotype and GA + GG genotypes male carriers with MI aged <50 in median triglyceride (TG) level (2.0 vs. 1.7 mmol/l respectively, p = 0.023). CONCLUSIONS: Our findings suggest a possible role of ESR2 G1730A variant as the risk factor of MI in a young age not as an independent but a potential risk factor associated with TG level in men but not in women.

Adiponectin gene variants and decreased adiponectin plasma levels are associated with the risk of myocardial infarction in young age.

The aim of the study was to investigate the role of adiponectin and 5 variants of its gene in the risk of premature myocardial infarction (MI). The studied group (MI<50) consisted of 158 young patients (125 men) aged <50 with MI. The control groups consisted of 155 healthy people (97 men), aged <50 and 202 patients (130 men) aged ≥50 with MI (MI≥50). There were statistically significant differences between MI<50 patients and healthy control group in the prevalence of rs17300539:G>A (AA genotype: 19.3% vs. 0%, p<0.0001) and rs72563731:C>T variants (CC genotype: 81.5% vs. 15.9%, p<0.0001) and between MI<50 and MI≥50 patients in variants: rs17300539:G>A (AA genotype: 19.3% vs. 0.5%, p<0.0001), rs72563731:C>T (CC genotype: 82.1% vs. 60.8%, p<0.0001), rs1501299:G>T (TT genotype: 6.8% vs. 14.9%, p=0.019) and rs822387:T>C (genotype CC: 1.5% vs. 0%, p=0.017). Multivariate analysis showed a significantly higher risk of MI in young CC carriers of rs72563731:C>T and in young AA carriers of rs17300539:G>A. Total and HMW adiponectin plasma levels have been significantly lower in MI<50 patients in comparison to MI≥50 patients (p=0.001 and p=0.001, respectively) and to healthy subjects (p=0.009 and p=0.01, respectively). Our study indicates the possible role of adiponectin and its genetic variants in MI in young age.

The -351A/G polymorphism of ESR1 is associated with risk of myocardial infarction but not with extreme longevity.

BACKGROUND: Women live longer than men. Some possible reasons for this advantage are the protection provided by high concentrations of 17ß-estradiol (E2) during the premenopausal period and polymorphic variants of the estrogen receptors (ERs), which mediate various cardiovascular functions of E2. METHODS: We tested whether the -351A/G and -397T/C polymorphisms of the ERα-encoding ESR1 were associated with extreme longevity. The genomic DNA of 148 centenarians (C), 414 young controls (Y), and 208 myocardial infarction patients (MI) was analyzed by RFLP-PCR. RESULTS: Both polymorphisms were equally distributed in the Y, C, and in centenarians never diagnosed with MI (HC). In centenarians, none of these polymorphisms was associated with a particular lipid profile. The AA genotype of the -351A/G polymorphism was less frequent in the C, HC and Y groups than in MI patients (p=0.058, p=0.021, and p=0.004, respectively). In MI patients, the GG genotype of the -351A/G polymorphism was associated with significantly lower mean total cholesterol, LDL, and HDL levels compared to the AG (p=0.0194, p=0.0213, and p=0.0367, respectively) and AA genotypes (p=0.0014, p=0.0078, and p=0.0448, respectively). CONCLUSIONS: The -351A/G ESR1 polymorphism might be associated with MI, but not with extreme longevity.

Human breast cancer tissue expresses high level of type 1 5'-deiodinase.

Type 1 5'-deiodinase is one of two isoenzymes that participate in conversion of prohormone thyroxine into triiodothyronine (T3). A decrease in type 1 5'-deiodinase expression was observed in renal clear cell carcinoma, thyroid cancer, and lung cancer. The aim of this study was to evaluate type 1 5'-deiodinase activity and mRNA level in breast cancer tissue and non-cancerous surrounding breast tissue. Material was collected from 36 patients undergoing radical mastectomy or local tumor resection. In all non-cancerous breast tissues, type 1 50-deiodinase activity was found to be at a very low or immeasurable level, and type 1 5'-deiodinase mRNA was detected only in 2 out of the 36 samples. By contrast, 20 out of the 36 breast cancer tissues, mainly grades G1 and G2, expressed abundant type 1 5'-deiodinase activity and/or a high mRNA level. Our data demonstrated the presence of type 1 5'-deiodinase in well-differentiated breast cancer tissue. High enzymatic activity of type 1 50-deiodinase can potentially lead to an increase in the production of T3, which may affect target gene transcription, including genes responsible for energy expenditure, growth, differentiation, and proliferation.

[Thyroid transcription factors involved in the thyroid hormones biosynthesis]. / Tarczycowe czynniki transkrypcyjne zwiazane z procesem biosyntezy hormonów tarczycy.

The thyroid hormone biosynthesis is dependent on the level of the expression and the correct action of the basic proteins involved in this process: TSH receptor (TSH-R), sodium-iodine symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO) and iodothyronine deodinases type 1 (D1) and type 2 (D2). Transcription of the genes coding these proteins is regulated by TSH via cAMP cascade. Despite the thyroid-specific transcription factors are necessary for the transcription regulation of TSH-R, NIS, TG, TPO, DIO1 and DIO2 genes. Three thyroid transcription factors Titf1/Nkx2-1, Foxel and Pax8 seem to be essential for thyroid development, growth and function. Disturbances of the expression of these transcription factors and their co-operation could be responsible for the congenital thyroid gland disorders as well as in thyroid cancerogenesis.

Disturbed expression of type 1 and type 2 iodothyronine deiodinase as well as titf1/nkx2-1 and pax-8 transcription factor genes in papillary thyroid cancer.

Type 1 and type 2 iodothyronine 5' deiodinases (D1 and D2, respectively) catalyze the conversion of thyroxine (T(4)) to triiodothyronine (T(3)). Similar to other genes crucial for T(3) generation, D1 and D2 expression might be disturbed in papillary thyroid cancer (PTC) possible as a result of impairments in thyroid transcription factors Titf1/Nkx2-1 and Pax-8. The aim of the study was to investigate changes in the expression of D1 and D2 in PTC compared to changes in the expression of Titf1/Nkx2-1 and Pax-8. Although D1 and D2 activities were decreased in tumor samples (PTC) compared to control C samples (tissues from a nontumorous part of the gland), the differences were not statistically significant. Contrary to that, their mRNA levels were significantly decreased in PTC samples compared to C samples (p = 0.017 and p = 0.012, respectively). Interestingly there was clear discrepancy between enzymatic activity and mRNA level of both deiodinases. There was a statistically significant correlation between D1 and Pax-8 (r = 0.464, p = 0.039), D2 and Pax-8 (r = 0.461, p = 0.041), D2 and Titf1/Nkx2-1 mRNA levels (r = 0.526, p = 0.017). Our results show that changes in D1 and D2 expression in PTC, including the discrepancy between deiodinases activity and mRNA level, might possibly related to impaired Titf1/Nkx2-1 and Pax-8 action.

Thyroid sialyltransferase mRNA level and activity are increased in Graves' disease.

Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor.

Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease.

Transcription factors TTF-1 and Pax-8 control the expression of thyroid-specific genes crucial for thyroid function. It has been postulated that they may play a role in thyrotropin (TSH)-mediated augmentation of gene expression observed in some thyroid diseases including Grave's hyperthyroidism. Recently, we and others described the expression of two genes participating in thyroid hormone metabolism type I and type II deiodinase (D1 and D2, respectively) that are upregulated by TSH, although the mechanisms responsible for this effect are likely to be different. The aim of this study was to investigate whether there is a correlation between TTF-1 and Pax-8 mRNA levels and type I or type II 5' deiodinases expression in Graves' disease. D1 activity and mRNA level, as well as D2 activity and mRNA level, were significantly increased in Graves' disease in comparison to control tissues. D1, but not D2, activity correlated with its mRNA level in Graves' disease and toxic multinodular goitre. The TTF-1 mRNA level was not different between Graves' disease and control thyroids and no correlation between TTF-1 mRNA level and either D1 or D2 mRNA levels were found. The Pax-8 mRNA level was significantly increased in Graves' disease in comparison to control tissues and correlated with D2, but not D1, mRNA levels among all investigated groups of tissues. Our data suggest that transcription factor Pax-8 could be involved in the upregulation of D2 expression in the thyroid of Graves' patients.