(INKUBÁTOR program of the Department of Molecular Biology)
(TKP2021-EGA-24)
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.
