The combined prevalence of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus is 10.5% worldwide and this is constantly increasing. The pathophysiology of the diseases include disturbances of the lipid metabolism, in which acyl-CoA desaturases play a central role as they synthesize unsaturated fatty acids, thereby providing protection against lipotoxicity. The stearoyl-CoA desaturase-5 (SCD5) isoform has received little scientific attention. We aimed to investigate the SCD5 promoter and its polymorphisms in vitro, in silico and in a case-control study. The SCD5 promoter region was determined by a luciferase reporter system in HepG2, HEK293T and SK-N-FI cells and it was proved to be cell type-specific, but it was insensitive to different fatty acids. The effect of the SCD5 promoter polymorphisms rs6841081 and rs3811792 was tested in the transfected cells. The T allele of rs3811792 single nucleotide polymorphism (SNP) significantly reduced the activity of the SCD5 promoter in vitro and modified several transcription factor binding sites in silico. A statistically significant association of rs3811792 SNP with T1DM and T2DM was also found, thus supporting the medical relevance of this variation and the complexity of the molecular mechanisms in the development of metabolic disorders. In conclusion, the minor allele of rs3811792 polymorphism might contribute to the development of diabetes by influencing the SCD5 promoter activity.

Background Cardiac magnetic resonance (CMR) examinations have an essential role in the diagnosis of myocardial diseases with left ventricular (LV) hypertrophy; however, limited data are available from CMR-based feature-tracking strain analysis in this patient population. The aim of our study was to investigate the differential diagnostic and prognostic importance of feature-tracking strain analysis in patients with LV hypertrophy caused by myocardial disease. Methods We investigated 404 patients who underwent CMR examination and were diagnosed with myocardial disease causing LV hypertrophy. Hypertrophic cardiomyopathy (HCM) was detected in 330 patients, cardiac amyloidosis (CA) in 46 patients, Fabry disease (FD) in 12 patients, and endomyocardial fibrosis (EMF) in 16 patients. LV strain analysis was performed with feature-tracking. Global longitudinal (GLS), circumferential (GCS) and radial (GRS) LV strain parameters were measured. Strain values for the six basal, six midventricular, and five apical segments were averaged to obtain regional longitudinal and circumferential strain values (basal LS, midventricular LS, apical LS, basal CS, midventricular CS, apical CS). The apex-to-base regional LS and CS ratios were calculated as apical LS/basal LS and apical CS/basal CS, respectively. To assess global dyssynchrony, mechanical dispersion (MD) was measured. The all-cause mortality of the patients was analyzed. Results In the differentiation of CA from HCM, GLS had the highest sensitivity with a cutoff of more than −23%, and basal LS and basal CS had the highest specificity with a cutoff of more than −16% and −38%, respectively (p<0.001). FD patients had the lowest longitudinal and circumferential MD values, meaning that compared to that of other patients with LV hypertrophy, global dyssynchrony is least pronounced in this patient population (p<0.01). EMF patients had impaired global and regional CS and the lowest apex-to-base CS and LS ratios. CA patients had the highest apex-to-base CS and LS ratios, suggestive of apical sparing (p<0.001). CA patients had the worst prognosis; the significant independent predictors of mortality were a diagnosis of CA, the LV stroke volume index and basal LS (p<0.01). Conclusions Myocardial diseases with left ventricular hypertrophy have remarkable differences in CMR-based strain characteristics which can be helpful in the differential diagnosis and provides incremental information on adverse outcomes. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Development and Innovation Fund of Hungary, Ministry for Innovation and Technology in Hungary

Alternative splicing (AS) is a major means of post-transcriptional control of gene expression, and provides a dynamic versatility of protein isoforms. Cancer-related AS disorders have diagnostic, prognostic and therapeutic values. Changes in the expression and AS of human stearoyl-CoA desaturase-5 (SCD5) are promising specific tumor markers, although the transcript variants (TVs) of the gene have not yet been confirmed. Our in silico, in vitro and in vivo study focuses on the distribution of SCD5 TVs (A and B) in human tissues, the functionality of the relevant splice sites, and their modulation by certain single-nucleotide variations (SNVs). An order of magnitude higher SCD5A expression was found compared with SCD5B. This unequal splicing is attributed to a weaker recognition of the SCD5B-specific splicing acceptor site, based on predictions confirmed by an optimized minigene assay. The pronounced dominance of SCD5A was largely modified (rs1430176385_A, rs1011850309_A) or even inverted (rs1011850309_C) by natural SNVs at the TV-specific splice sites. Our results provide long missing data on the proportion of SCD5 TVs in human tissues and reveal mutation-driven changes in SCD5 AS, potentially affecting tumor-associated reprogramming of lipid metabolism, thus having prognostic significance, which may be utilized for novel and personalized therapeutic approaches.