Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), thiol (p < 0.001), NO (p < 0.01), and PAB (p < 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (p < 0.001) and PAB (p < 0.001) when compared to healthy subjects. Elevated levels of MDA (p < 0.001) and PAB (p < 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979; p = 0.033), and MDA (OR: 0.996; p = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished. Conclusion: Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.

IntroductionWe aimed to evaluate the serum level of miRNA-27 (miRNA-27a and miRNA-27b) expression in familial hypercholesterolemia. miRNA-27a/b is a prominent regulator of cholesterol and lipid metabolism and essential miRNA in suppressing cholesterol efflux.Material and methodsmiRNA-27a/b levels in serum were compared between 39 patients with heterozygous familial hypercholesterolemia (HeFH=20) and homozygous familial hypercholesterolemia (HoFH=19), and 20 healthy subjects. Here, we set out to further characterize the role of miRNA-27a/b in the severity of FH by evaluating the expression of miRNA-27a/b in these subjects. The expression level of miRNA-27a/b was measured using real-time PCR in the three mentioned groups.ResultsmiRNA-27a/b expression in patients with FH (fold change: 2.21±0.69, P=0.001), as well as a subgroup of homozygous FH (fold change: 3±1.19, P=0.001), was significantly higher compared to healthy people. There was a borderline non-significant difference between the heterozygous FH and groups (FC: 1.62±0.46, P=0.059). In the comparison between HoFH and HeFH, the HoFH group had a higher significant level of miRNA-27a/b expression (FC: 1.84±1.19, P=0.009). Furthermore, the expression level was also examined in terms of gender, which was found to be significant in the comparison between the male FH and control groups. However, this difference was not seen between female groups.ConclusionsOur research exhibited that miRNA-27a/b has a higher expression in patients with FH than in healthy individuals. Moreover, in comparison with HoFH and HeFH groups, the former had a higher expression level of miRNA-27a/b, which indicates the potential of miRNA-27a/b as a candidate marker for the severity of disease in individuals with FH.