Investigating the expression level of miR-17-3p, miR-101-3p, miR-335-3p, and miR-296-3p in the peripheral blood of patients with acute myocardial infarction.

The role of inflammation has been proven in acute myocardial infarction (AMI) pathogenesis. Due to the effect of NLRP3 gene expression in the inflammation process of MI, we aimed to explore the expression changes and diagnostic power of four inflammation-related miRNAs including miR-17-3p, miR-101-3p, miR-335-3p, miR-296-3p and their potential target, NLRP3, in ST-segment elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) patients as two major classes of AMI. The expression level of these genes were evaluated in 300 participants equally divided into three groups of STEMI, NSTEMI, and control using quantitative real-time PCR. The expression level of NLRP3 was upregulated in STEMI and NSTEMI patients compared to control subjects. Besides, the expression levels of miR-17-3p, miR-101-3p, and miR-296-3p were significantly downregulated in STEMI and NSTEMI patients compared to controls. The increased expression of NLRP3 had a very strong inverse correlation with miR-17-3p in patients with STEMI and with miR-101-3p in the STEMI and NSTEMI patients. ROC curve analysis showed that the expression level of miR-17-3p had the highest diagnostic power for discrimination between STEMI patients and controls. Remarkably, the combination of all markers resulted in a higher AUC. In summary, there is a significant association between the expression levels of miR-17-3p, miR-101-3p, miR-335-3p, miR-296-3p, and NLRP3 and the incidence of AMI. Although the miR-17-3p expression level has the highest diagnostic power to distinguish between STEMI patients and control subjects, the combination of these miRNAs and NLRP3 could serve as a novel potential diagnostic biomarker of STEMI.

Promoter methylation and functional variants in arachidonate 5-lipoxygenase and forkhead box protein O1 genes associated with coronary artery disease.

Coronary artery disease (CAD) is a multifactorial chronic inflammatory disease, which is the most common form of heart disease. This is one of the main causes of death in the United States. Inflammation is one of the key drivers of atherosclerotic plaque development. Forkhead box protein O1 (FOXO1s) family and 5-lipoxygenase make an important contribution to atherosclerosis. The aim of this study was to investigate the methylation pattern and polymorphism analysis of FOXO1 and arachidonate 5-lipoxygenase (ALOX5) promoter genes. We studied 50 patients with CAD and 50 age- and sex-matched healthy controls by high resolution melt technique. Overall, we found significant differences between patients and controls in terms of the promoter methylation of ALOX5 (P > 0.05). But there was no significant difference in FOXO1 promoter methylation between patient and controls. Single nucleotide polymorphisms genotyping of rs12762303 and rs2297627, in ALOX5 and FOXO1 genes were demonstrated a significant correlation between mutant allele and the risk of CAD, respectively. Furthermore, there were significant associations between CT + CC genotype and ALOX5 expression. Our findings demonstrated functional effects of single nucleotide polymorphisms (SNPs) and DNA methylation in ALOX5 on mentioned genes expression and they resulted in CAD progression.

Reverse expression pattern of sirtuin-1 and histone deacetylase-9 in coronary artery disease.

BACKGROUND: SIRT1 and HDAC 9 genes are related to inflammation and may contribute to the pathogenesis of coronary artery disease (CAD). We aimed to evaluate the expression level, methylation profile and polymorphisms of these genes in CAD patients. METHODS: In this study, 50 CAD patients and 50 healthy individuals were recruited. The expression level change was evaluated using the TaqMan Real-Time PCR method. The methylation of genes promoter and genotyping of polymorphisms were evaluated by the HRM. RESULTS: The expression level of SIRT1 was reduced while the HDAC9 expression level showed a significant elevation (p < .001). The SIRT1 gene promoter was hypomethylated and the HDAC9 gene promoter was hypermethylated in CAD patients. Also, CG + GG genotype in SIRT1 and both genotypes in the HDAC9 gene were associated with expression change. CONCLUSIONS: SIRT1 and HDAC9 genes, expression changes can be suggested as a potential biomarker for CAD detection.

MicroRNA-copy number variations in coronary artery disease patients with or without type 2 diabetes mellitus.

BACKGROUND: An important cause of Coronary Artery Disease (CAD) is Type 2 Diabetes Mellitus (T2DM). The aim of this study was the evaluation of copy number variations (CNVs) of hsa-miR-93, hsa-miR-122, hsa-miR-192 in CAD patients with or without T2DM. METHODS: CNVs of three micro-RNAs in 50 CAD patients and 50 non-CAD subjects both with and without diabetes were evaluated by real-time PCR and compared in three comparison groups namely 1, 2 and 3 (including comparison between CAD and non-CAD, diabetic CAD and non-diabetic CAD and between diabetic CAD and diabetic non-CAD subjects, respectively). RESULTS: There were significant differences in CNVs of hsa-miR-93 between cases and controls in comparison groups 1 and 3 (p = .0310 and .0232, respectively), for hsa-miR-122 in all comparison groups, and for hsa-miR-192 in comparison group 3 (p = .0181). CONCLUSION: We showed the association of these microRNA-CNVs with CAD, T2DM or both simultaneously.

Comparative Assessment of Tear Function Tests, Tear Osmolarity, and Conjunctival Impression Cytology between Patients with Pterygium and Healthy Eyes.

PURPOSE: To compare histologic abnormalities of tear film and tear osmolarity between normal eyes and eyes with pterygium. METHODS: This was a prospective, hospital-based, case-control study involving 95 patients (65 men, 30 women) with unilateral pterygium. The tear meniscus height (TMH), Schirmer's test-1 (SCH-1) score, Rose Bengal staining (RBS) score, tear film breakup time (TBUT), tear osmolarity (TO), and conjunctival impression cytology (CIC) were assessed in both eyes. The Chi-square and Student's t-tests were used to compare the results between the two groups. P values <0.05 were considered statistically significant. RESULTS: The mean patient age was 50.9 years, with the largest age group being the 45-55 year-old bracket across both genders. Most patients (82.1%) had nasal pterygium, and 80% were involved in outside activities. The mean assessment values in the case and control groups were as follows: TMH, 0.21 vs. 0.24 mm; SCH-1, 13.2 vs. 17.8 mm; RBS, 4.38 vs. 2.51 points; TBUT, 8.7 vs. 13.2 seconds; TO, 306 vs. 299 mOsm/L (P < 0.001 in all cases). The proportions of abnormal assessment values in the case and control groups were as follows: TMH, 82.1% vs. 3.16%; SCH-1, 20% vs. 2.1%; RBS, 30.53% vs. 4.22%; TBUT, 61.05% vs. 6.3%; TO, 10.52% vs. 1.05%; CIC, 33.7% vs. 7.37% (P < 0.05 for all comparisons). CONCLUSION: This study showed that the quantity and quality of tear film, as well as the number of goblet cells, decreased, but the tear osmolarity increased in eyes with pterygium. Furthermore, the TMH, RBS results, TBUT, and CIC have more precise state of the patient's tear condition with the disease of the pterygium.

Association of interleukin-6 (rs1800796) but not transforming growth factor beta 1 (rs1800469) with serum calcium levels in osteoporotic patients.

BACKGROUND: Osteoporosis is a multifactorial disease with a strong genetic influence. Recent studies have demonstrated that cytokines, such as TGF-ß1 and interleukin 6 (IL-6) play complex roles in the normal bone metabolism and pathophysiology of osteoporosis. Here, we investigated the roles of 2 polymorphisms mapping to the promoters of TGF-ß1and IL-6 genes on the genetic susceptibility to osteoporosis as well as calcium and vitamin D levels. METHODS: A cohort of 297 elderly participants in northern Iran comprising 181 osteoporotic patients (mean age ±â€¯SD, 68.36 ±â€¯7.21 years) and 116 unrelated healthy controls (mean age ±â€¯SD, 64 ±â€¯5.44 years) was studied for TGF-ß1(C-509T) and IL-6 (G-634C) polymorphisms using PCR-RFLP method. RESULTS: A significant relationship was observed between calcium level and IL-6 genotypes in osteoporotic males (P = 0.011) and females (P = 0.020). No significant differences were observed between osteoporotic and control groups with respect to allele frequency or genotype distribution based on the 2 selected polymorphisms under different genetic models. The results remained the same after comparing the BMD values of either the femur neck or lumbar spine with the genotypes of the elderly men and women when analyzed separately. CONCLUSION: IL-6 genotype influences serum calcium levels in osteoporotic patients. The lack of association between the common genetic variations of TGF-ß1 and IL-6 genes, and BMD highlights the complex genetic background of osteoporosis in the north of Iran.

Analysis of Two CDKN2B-AS Polymorphisms in Relation to Coronary Artery Disease Patients in North of Iran.

Coronary artery disease (CAD) including myocardial infarction (MI) as its complication, is one of the most common heart diseases worldwide and also in Iran, with extremely elevated mortality. CAD is a multifactorial disorder. Twin and family studies at different loci have demonstrated that genetic factors have an important role in the progression of CAD. Many studies have reported a significant association of CDKN2B-AS, also known as ANRIL which is located within the p15, p16, p14 gene cluster at 9p21 locus, with cardiovascular diseases as well as many other diseases like diabetes and cancers. This study investigated two polymorphisms rs10757274 and rs1333042 of CDKN2B-AS gene at 9p21 locus. 205 subjects, comprising 102 controls and 103 CAD patients were genotyped by TaqMan probe real time PCR technique and haplotypes were examined. This study confirmed the association of rs10757274 variants with CAD in Iranian patients (P= 0.003) but genotype and allele distributions of CAD and control groups showed no significant association for the rs1333042. However, frequency of the [G;G] haplotype of these two SNPs was significantly higher in CAD group (P= 0.0002, Odds Ratio = 3.1, 95% CI = 1.7-5.7). Our finding suggests that [G; G] haplotype of rs10757274 and rs1333042 may be considered as a genetic risk factor for susceptibility to CAD in Iranian patients.

Osteoporosis: A Silent Disease with Complex Genetic Contribution.

Osteoporosis is the most common multifactorial metabolic bone disorder worldwide with a strong genetic component. In this review, the evidence for a genetic contribution to osteoporosis and related phenotypes is summarized alongside with methods used to identify osteoporosis susceptibility genes. The key biological pathways involved in the skeleton and bone development are discussed with a particular focus on master genes clustered in these pathways and their mode of action. Furthermore, the most studied single nucleotide polymorphisms (SNPs) analyzed for their importance as genetic markers of the disease are presented. New data generated by next-generation sequencing in conjunction with extensive meta-analyses should contribute to a better understanding of the genetic basis of osteoporosis and related phenotype variability. These data could be ultimately used for identifying at-risk patients for disease prevention by both controlling environmental factors and providing possible therapeutic targets.