Familial combined hyperlipidemia: An overview of the underlying molecular mechanisms and therapeutic strategies.

Among different types of dyslipidemia, familial combined hyperlipidemia (FCHL) is the most common genetic disorder, which is characterized by at least two different forms of lipid abnormalities: hypercholesterolemia and hypertriglyceridemia. FCHL is an important cause of cardiovascular diseases. FCHL is a heterogeneous condition linked with some metabolic defects that are closely associated with FCHL. These metabolic features include dysfunctional adipose tissue, delayed clearance of triglyceride-rich lipoproteins, overproduction of very low-density lipoprotein and hepatic lipids, and defect in the clearance of low-density lipoprotein particles. There are also some genes associated with FCHL such as those affecting the metabolism and clearance of plasma lipoprotein particles. Due to the high prevalence of FCHL especially in cardiovascular patients, targeted treatment is ideal but this necessitates identification of the genetic background of patients. This review describes the metabolic pathways and associated genes that are implicated in FCHL pathogenesis. We also review existing and novel treatment options for FCHL. © 2019 IUBMB Life, 71(9):1221-1229, 2019.

Expression Analysis of Five Different Long Non-Coding Ribonucleic Acids in Nonsmall-Cell Lung Carcinoma Tumor and Tumor-Derived Exosomes.

Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx = 3.64, p = 0.028), HNF1A-AS1 (REx = 2.97, p = 0.041), and HOTAIR (REx = 2.9, p = 0.0389) were upregulated, and the expressions of HMlincRNA717 (REx = −4.56, p = 0.0012) and LINCRNA-p21 (REx = −5.14, p = 0.00334) were downregulated in tumor tissue in contrast to ANCT. Moreover, similar statistical differences were seen in the exosome-derived RNA of tumor tissues in contrast to ANCT samples. A panel of the five lncRNAs demonstrated that the area under the curve (AUC) for exosome and tumor was 0.937 (standard error: 0.012, p value < 0.0001). LncRNAs GHSROS, HNF1A-AS1, and HOTAIR showed high expression in tumor tissue and exosome content in NSCLC, and a panel that consisted of all five lncRNAs improved diagnosis of NSCLC.

Genetic variants of the phenylalanine hydroxylase gene in patients with phenylketonuria in the northeast of Iran.

Background Phenylketonuria (PKU) is a common metabolic disorder with great burden if left untreated or undiagnosed. Genetic variations in the phenylalanine hydroxylase (PAH) gene may be widely varied across different regions of a country. By knowing the most common mutations, diagnostic work-ups will be offered sooner and with lower costs for patients. The present study defines the most common genetic variations in the PAH gene in Khorasan province of Iran. Methods The present cross-sectional study took place in Khorasan province of Iran within a 6-year period starting from 2012 to 2018. Every patient who had been referred as suspicious PKU cases or referred for prenatal diagnosis was included in the present study. Results A total number of 122 individuals with a mean age of 26.22 years were enrolled in the present study. The most frequent genetic variations in the PAH gene were c.1066-11G > A and c.143 T > C. Exon 7 carried the most genetic variations compared to any single exon. Also, three patients had compound heterozygous status for c.727 C > T/c.1066-11 G > A in exon 7 and 11 of the PAH gene. Conclusions Mutations in the PAH gene are widely varied among different populations, and our results confirmed this fact. Determination of the most prevalent mutations and polymorphisms in each region will reduce the time and cost of diagnosing such preventable diseases and will therefore reduce the disease burden.

Inverse Relation between MxA Gene Expression and Age in Multiple Sclerosis Patients Reveals a Gender Difference in Response to Interferon Therapy.

Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central nervous system that women are at a higher risk to acquire than men. Myxovirus resistance protein A (MxA) is used as a predictive marker of bioactivity of interferon-beta (IFN-ß) therapy in MS patients. This study was undertaken in west of Iran to investigate gender differences in the expression level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-ß therapy, compared with untreated normal individuals. The expression level of the MxA gene in RRMS samples were compared to untreated normal individuals using the extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and 50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15 negative and responded to IFN-ß with a normal vitamin D level. The level of MxA gene expression was measured by quantitative RT-PCR. The levels of gene expression were decreased in RRMS patients compared with normal counterparts (p=0.025). This decrease was significant in females (p=0.009) compared to males (p>0.05). The level of expression varied across different female age-groups with no significant difference in women younger than 30 years, but a significant decrease in expression in women between 30 to 40 years or above 40 years of age was seen. There was neither linear correlation between the MxA expression level and risk of expanded disability status scale of Kurtzke (EDSS); nor were there any significant correlation between expression status of MxA and duration of the disease. In conclusion, the decrease in the level of MxA expression in MS patients treated with IFN-ß when compared to normal individuals was significantly lower in females than males.  This demonstrated a gender bias in the response to IFN-ß therapy that will need to be confirmed and further investigated in more detail.