Relation of genetic polymorphisms in microRNAs with diastolic and systolic function in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) has high risk of developing cardiac dysfunction, increasing of either cardiovascular death or hospitalization for heart failure. MicroRNAs (miRNA) affect cardiac function of T2DM. The aim of this study was to investigate the relationships between five miRNA single nucleotide polymorphisms (SNP) and diastolic and systolic function of T2DM. METHODS AND RESULTS: Three hundred untreated T2DM subjects were included. Each subject underwent SNP genotyping, conventional echocardiography, tissue doppler imaging, and speckle tracking imaging. The effects of miRNA SNPs on diastolic and systolic function were evaluated. The diastolic function of T2DM subjects with miR-133a-1-rs8089787 wild genotype or let-7f-rs10877887 variant genotype was lower than those with miR-133a-1-rs8089787 variant genotype or let-7f-rs10877887 wild genotype, manifesting as higher left atrial volume index, lower mean E', and higher E/E' (P < 0.05). There were no significant effects of miR-133a-2-rs13040413, let-7a-1-rs13293512 and miR-27a-rs895819 on the diastolic function of T2DM subjects (P > 0.05). These five miRNA SNPs had no effect on the systolic function of T2DM subjects (P > 0.05). CONCLUSIONS: MiRNA-133a-1-rs8089787 and let-7f-rs10877887 were associated with impaired cardiac diastolic function in T2DM. The findings may be a promising therapeutic targets for preventing diastolic dysfunction in T2DM.

Identification of three novel pathogenic mutations in sarcomere genes associated with familial hypertrophic cardiomyopathy based on multi-omics study.

BACKGROUND: Familial hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death, but exhibits heterogeneous clinical features. A major research focus is to identify specific ultrasonic phenotypes, and causal gene mutations, as well as to elucidate the possible metabolic pathogenic effects in familial HCM through multi-omics study. METHODS: Nine members of two familial HCM pedigrees were enrolled in this study. Their clinical data were collected, and the data of multiparameter ultrasound, whole-exome sequencing, and untargeted metabolomics were analyzed. RESULTS: We identified three novel pathogenic sarcomere gene mutations, TNNT2-rs397516484, MYH6-rs372446459 and MYBPC3-rs786204339 in two familial HCM pedigrees. The proband of Family 1 and his father carried TNNT2-rs397516484 and MYH6-rs372446459 missense mutations, while the proband of Family 2 and her brother carried MYBPC3-rs786204339 frameshift mutation. They presented with heart failure and abnormal electrocardiogram, accompanied by diastolic and systolic dysfunction and impaired myocardial work. They also showed disturbances of carbohydrate metabolism, including the citrate cycle (TCA cycle), glycolysis/gluconeogenesis, fructose and mannose metabolism, pentose and glucuronate interconversions and amino sugar and nucleotide sugar metabolism. CONCLUSIONS: Novel TNNT2-rs397516484, MYH6-rs372446459, and MYBPC3-rs786204339 are pathogenic sarcomere gene mutations in familial HCM, leading to decreased cardiac function and metabolic disturbances of carbohydrate metabolism, which have important implications for biologically defined diagnoses and precision medicine.

Invasive cardiac lipoma diagnosis based on echocardiography: Case report and literature review.

Echocardiography is first-line examination of cardiac tumors. We report the case of a 25-year-old woman with a right atrial transmural invasive lipoma, and we review 58 published reports of primary cardiac invasive lipomas detected by echocardiography. We summarize the ultrasonographic characteristics and main sites of development, and examine the "invagination hypothesis". Echocardiography appears valuable for early detection, intraoperative monitoring, and postoperative follow-up of invasive cardiac lipomas.

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population.

Introduction: MicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms. Methods: Five SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated. Results: In overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele. Conclusion: MiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.

The Relationship of Ankylosing Spondylitis and Subclinical Atherosclerosis: A Systemic Review and Meta-Analysis.

Cardiovascular disease has become the first cause of death for patients with ankylosing spondylitis (AS). However, the relevant data is limited and the relationship between AS and subclinical atherosclerosis remains questionable. Therefore, we assessed the relationship between subclinical atherosclerosis and AS in this meta-analysis. We synthesized the primary data on flow-mediated vasodilation (FMD), carotid intima media thickness (cIMT), or pulse wave velocity (PWV)-related studies involving AS and using searched electronic databases. Not only were heterogeneity tests, publication bias, and sensitivity analysis performed overall, but also subgroup analysis and meta-regression grouped by measuring site, region, age, sex, and sample size were also carried out. A total of 35 articles involving 1535 patients with AS and 1347 normal controls were included. Significantly increased cIMT (weighted mean difference [WMD]; 95% confidence interval [CI]) = 0.071 [0.048-0.094]), PWV (WMD [95%CI] = 0.910 [0.464-1.356]), and decreased FMD (WMD [95%CI] = -4.459 [-8.389 to -0.529]) were observed in patients with AS compared to controls. The funnel plots or Egger test or Begg test showed no significant publication bias (all P > .05). Sensitivity analysis did not show statistical significance. We conclude that patients with AS have a higher risk of subclinical atherosclerosis. Early screening and intervention deserves consideration.

MicroRNA single-nucleotide polymorphisms and diabetes mellitus: A comprehensive review.

Diabetes mellitus (DM) has become the third major chronic non-communicable disease affecting global public health, following cancer and cardiovascular and cerebrovascular diseases. Although previous studies have found a correlation between microRNA (miRNA) and the development of DM, thus far, most reviews have focused on the studies describing the changes in miRNA expression profiles and the mechanisms by which miRNAs-induce DM. However, reviews summarizing the effect of miRNA single-nucleotide polymorphisms on the developmental stages of DM and its complications are still needed. Studies on the variation of miRNAs will not only help to further understand the role that genetic factors play in DM, but will also have important implications for treatment and disease prognosis.