Association of matrix Gla protein gene allelic polymorphisms (G(-7)→A, T(-138)→C and Thr(83)→Ala) with acute coronary syndrome in the Ukrainian population.

BACKGROUND: Several allelic variants of matrix γ-carboxyglutamic acid protein (MGP) can differentially affect the development of certain forms of ischemic heart disease depending on specific characteristics of each population. OBJECTIVE: To study the distribution of allelic variants of MGP promoter T(-138)→C (rs1800802) and G(-7)→A (rs1800801), and Thr(83)→Ala exon 4 (rs4236) polymorphisms in a Ukrainian population of patients with acute coronary syndrome (ACS). METHODS: Polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis were used to detect the above-mentioned variants of the MGP gene in 115 patients with ACS and in 140 essentially healthy individuals. RESULTS: The distribution of homozygous carriers of a major allelic variant, and heterozygous and homozygous minor allele variants of the T(-138)→C MGP promoter polymorphism in patients with ACS were 59.8%, 32.7% and 7.5%, respectively. The corresponding distributions of variants in the control group were 54.0%, 41.0% and 5.0%, respectively (P>0.05 [χ(2) test]). With respect to the G(-7)→A polymorphism, the respective distributions were 42.1%, 45.6% and 12.3%, compared with 50.7%, 45.0% and 4.3% in the control group, respectively (P<0.05). Finally, the respective distributions according to the Thr(83)→Ala exon 4 polymorphism were 42.6%, 43.5% and 13.9%, respectively, compared with 45.3%, 43.0% and 11.7% in the control group. Using logistic regression analysis, it was estimated that the A/A genotype (G(-7)→A polymorphism) was significantly (P=0.02) associated with ACS (OR 4.302 [95% CI 1.262 to 14.673]). CONCLUSION: The allelic A/A promoter variant of MGP G(-7)→A polymorphism can be considered a risk factor for ACS in the Ukrainian population.

Mature and immature microRNA ratios in cultured rat cardiomyocytes during anoxia-reoxygenation.

BACKGROUND: The critical role of microRNAs (miRNAs) in the global control of gene expression in the heart has recently been postulated; however, the mechanisms of miRNA regulation in cardiac pathology are not clear. OBJECTIVE: To evaluate the levels of miR-1, miR-208a and miR-29a expressed in neonatal rat cardiomyocytes during anoxia-reoxygenation (AR). METHODS: Reverse transcription coupled with real-time polymerase chain reaction was used to evaluate the level of mature and immature miRNAs in cardiomyocyte culture during AR. RESULTS: THE INITIAL LEVELS OF THE MATURE AND IMMATURE MIRNAS WERE DIFFERENT: mature - miR-1 7.46±4.440, miR-208a 0.02±0.015 and miR-29a 5.60±2.060; immature - miR-1 0.02±0.007, miR-208a 0.05±0.029 and miR-29a 0.01±0.008. The most prominent changes were observed for immature miRNAs during AR, with immature miR-1 and miR-29a expressed at significantly higher levels during remote reoxygenation (AR [0.5 h/24 h]) compared with control, while the level of expressed immature miR-208a was significantly decreased during acute reoxygenation (AR [0.5 h /1 h]) and returned to control levels during remote reoxygenation (AR [0.5h /24 h]). Also, the ratios of mature to immature miRNAs were significantly increased during acute reoxygenation for miR-1 and miR-208a, returning to control levels during remote reoxygenation, while for miR-29a, this ratio had the progressive tendency to decrease under AR. CONCLUSION: The discordance between the estimated levels of mature and immature miRNA during AR supports the hypothesis that transcriptional and post-transcriptional regulatory mechanisms at the miRNA level play a role in the response of cardiomyocytes to AR, and could be a contributing factor in the differential resistance of cardiomyocytes to AR.