Association of lncRNA PVT1 Gene Polymorphisms with the Risk of Essential Hypertension in Chinese Population

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results. PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH ( OR = 0.561 , 95% CI = 0.372 -0.846, P = 0.006 ), while rs80177647 TA genotype was associated with an increased risk ( OR = 2.236 , 95% CI = 1.515 -3.301, P < 0.001 ). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion. PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels.

High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides

Current real-time high-throughput Polymerase Chain Reaction (qPCR) methods do not distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009–2011), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92–101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of < 100 Colony-Forming-Units (CFU)/mL of sample. There was high concordance (Kappa = 0.73–0.92); sensitivity (85–100%) and specificity (96–100%) for Fluidigm compared with Quellung for serotyping 6A; 6B; 6C; 18C and 22F. Fluidigm distinguishes vaccine-serotypes 6A, 6B, 18C, next-generation PCV-serotype 22F and non-vaccine-serotypes 6C, 6D, 18A, 18B, 18F and 22A. Discriminating single serotypes is important for assessing serotype replacement and the impact of PCVs on vaccine- and non-vaccine serotypes.

SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two-Center Case-Control Study

Endothelial inflammation and vascular damage are essential risk factors contributing to hypertension. Suppressor of cytokine signaling 3 (SOCS3) is involved in the regulation of multiple inflammatory pathways. A large number of studies have shown that the anti-inflammatory effect of SOCS3 in hypertension, obesity, and allergic reactions has brought more insights into the inhibition of inflammation. Therefore, we selected a tagSNP of SOCS3 (rs8064821) to investigate whether they are contributing to the risk of hypertension in the Chinese population. In total, 532 patients with hypertension and 569 healthy controls were enrolled for two central of China. SOCS3 rs8064821 C>A polymorphism was genotyped using TaqMan assay. SOCS3 rs8064821 CA genotype was associated with an increased risk of hypertension ( OR = 1.821 , 95 % CI = 1.276 -2.600, P = 0.001 ). Rs8064821 A allele was associated with higher SOCS3 mRNA level in PBMCs from healthy donors. SOCS3 rs8064821 C>A polymorphism may contribute to the risk of hypertension in the Chinese population by regulating the expression of SOCS3.

Association Between Serum 5-methyltetrahydrofolate and Homocysteine in Chinese Hypertensive Participants With Different MTHFR C677T Polymorphisms: A Cross-sectional Study

Background and aims: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. Methods: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2,328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. Results: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was B 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: a = -0.50, P < 0.001; CC: c = -0.14, P = 0.087; CT: k = -0.20, P = 0.011; TT: g = -1.19, P < 0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference < 0.001) and genotype CT participants (P for difference < 0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). Conclusions: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was r 10 ng/mL , and this association was modified by MTHFR C677T.

Association Analysis of GDF5 and Contributing Factors in Developmental Dysplasia of the Hip in Infants

Background. Developmental dysplasia of the hip (DDH) is a developmental disorder which is reported to be associated with hip instability. When untreated, it can lead to irreversible joint damage. DDH is known to be a multifactorial disease involving genetic, mechanical and environmental factors. The greatest causative potential is attributed to the genetic component. Growth Differentiation Factor 5 (GDF5) is among the most studied genes associated with processes of regeneration and maintenance of joints. The aim of this work was to analyse the association of SNP rs143383 in the GDF5 gene and the occurrence of DDH, along with association with various contributing factors in the Caucasian population. Material and methods. A total of 118 samples were analysed for the presence of the mutation. DNA was isolated from all individuals from peripheral blood. SNP rs143383 in the GDF5 gene was genotyped using the TaqMan assay. A standard chi-square test was used to compare allele and genotype distributions in patients and healthy controls. Results. The association analysis of genotypes of DDH and rs143383 revealed a significant association. Also, the association of GDF5 and selected contributing factors was statistically significant in female gender (p=0.002), family history (p<0.001), count of pregnancy (p=0.009), laterality of hip involvement and initial US examination. Conclusions. 1. The results indicate an important effect of rs143383 polymorphism in the GDF5 gene on DDH development. 2. However, our results also suggest that rs143383 is not the only contributing factor in the genetic component of DDH.

LncRNA TARID Induces Cell Proliferation Through Cell Cycle Pathway Associated With Coronary Artery Disease

Background/Aim: Long noncoding RNA TARID (lncRNA TARID) can activate the tumor suppressor TCF21 in tumorigenesis by inducing promoter demethylation. However, the impact on lncRNA TARID and its variants of coronary artery disease (CAD) are poorly understood. Methods We performed a case-control study enrolling 949 case patients and 892 controls to assess genotype. Five variants were genotyped by TaqMan assay. 20 case patients and 20 controls were used to evaluate the expression of lncRNA TARID. The qRT-PCR and cell cycle analysis were applied to examined cell proliferation and cell distribution. Results This study indicated that rs2327433 GG genotype was associated with CAD risk adjusting for traditional risk factors (OR=2.74, 95%CI: 1.10-6.83, P=0.03). Our results analyses revealed that the genotype of rs2327433 was related to the proportion of CAD patients with left anterior descending artery disease and left circumflex artery disease (P=0.025 and P=0.025, respectively). The results showed that the minor allele frequency of rs2327433 was significantly correlated with the severity of the disease (P=0.029). The eQTL analysis showed that rs2327433 may affect the transcription factors TCF21 regulated by lncRNA TARID. We found that TARID silencing regulated the cell proliferation and altered cell cycle progression by induced upregulation of CDK1 and PCNA. Conclusions SNP rs2327433 in lncRNA TARID was associated with CAD risk and the severity of CAD in Chinese Han population. Furthermore, SNP rs2327433 may affect the expression of atherosclerosis-related transcription factor TCF21 regulated by lncRNA TARID. Finally, our study provided a new lncRNA-dictated regulatory mechanism participating in cell proliferation.

Correlation of circulating miRNA-33a and miRNA-122 with lipid metabolism among Egyptian patients with metabolic syndrome

Background Metabolic syndrome is defined as a group of interrelated biochemical, clinical, and metabolic factors that directly increase the risk of cardiovascular disease, obesity, and type 2 diabetes mellitus. MicroRNA-33a (miR-33a) and MicroRNA-122 (miR-122) play a crucial role in various biological processes by regulating the gene expression level through post-transcriptional mechanisms, and alterations of their levels are associated with lipid and glucose metabolic disorders. In the present study, we aimed to investigate the correlation of miR-33a and miR-122 with obesity indices and glycemic parameters in a cohort of Egyptian patients. Quantitative real-time polymerase chain reaction (RT-PCR) using TaqMan assay was carried out to estimate the expression levels of miR-33a and miR-122 in serum samples of 100 patients diagnosed as having metabolic syndrome and 50 healthy controls. All patients (100%) had type 2 diabetes (by both history and laboratory assessment) and 70% were obese (BMI ≥ 30 kg/m2). Results Compared to controls, patients had significantly higher serum expression level of miR-33a (p value < 0.001) and miR-122 (p value = 0.0016). miR-33a was less expressed (downregulation expression) with 0.8 fold change in the patient group (obese and diabetic) compared to healthy controls, while miR-122 was highly expressed (upregulation expression) in the patient group of patients with 1.9 fold change. Clinical parameters as body mass index (BMI), wrist circumference (Wc), weight (Wt), and height (Ht) (all p < 0.001); total cholesterol (TC) (p = 0.0115); and triglyceride (TG) (p = 0.0286), all were significantly higher in patients compared to the healthy group. Both miRNAs show statistically significant correlations with clinical and biochemical parameters (p < 0.001). Conclusions Circulating miR-33a and miR-122 might be convincing as possible biomarkers for the diagnosis of metabolic syndrome.

Polymorphism in the TP63 gene imparts a potential risk for leukemia in the North Indian population

Background: The role of single nucleotide polymorphism rs10937405 (C>T) of the TP63 gene in cancer including leu- kemia has previously been studied in different world populations; however, the role of this variant in leukemia in the North Indian population of Jammu and Kashmir is still unknown. Objectives: In the present study, we investigated the association of genetic variant rs10937405 with leukemic in the Jammu and Kashmir population. Methods: A total of 588 subjects, (188 cases and 400 controls) were recruited for the study. The rs10937405 variant was genotyped by using the real-time based TaqMan assay. Results: A statistically significant association was observed between the rs10937405 and leukemia [OR of 1.94 (95% CI 1.51-2.48), p=1.2x10-6]. Conclusion: The current study concludes that the rs10937405 variant is a risk factor for the development of leukemia in the population of Jammu and Kashmir, North India. However, it would be interesting to explore the contribution of this variant in other cancers as well. Our findings will help in the development of diagnostic markers for leukemia in the studied population and potentially for other North Indian populations. Keywords: Single Nucleotide Polymorphism (SNPs); Leukemia; North Indian population; Tumour suppressor (TP63); Linkage Disequilibrium (LD); Genome wide association studies (GWAS); Jammu and Kashmir (J &K).

Sleep duration, Health Promotion Index (HPI), sRAGE and ApoE-ε4 genotype are associated with telomere length (TL) in healthy elderly Australians

Significant alterations in sleep duration and/or quality of sleep become more pronounced as people get older. Poor sleep in elderly people is associated with adverse health outcomes and cellular ageing. We examined the relationship between TL and sleep duration, Health Promotion Index (HPI), and tested whether the presence of ApoE-ε4 allele impacts both sleep and TL. The present study was carried out in 174 healthy elderly subjects (21% male; mean age 53.79 years) from South Australia. Lymphocyte telomere length (TL) was measured by real-time qPCR and ApoE genotype was determined by TaqMan assay. HPI was calculated from a questionnaire regarding 8 lifestyle habits, including sleeping hours. Multivariate regression analysis was used to establish these associations adjusted for specified confounders. TL was found to be inversely associated with age (r = - 0.199; p = 0.008) and BMI (r = - 0.121; p = 0.11), and was significantly shorter in participants who slept for &lt;7 hours (p = 0.001) relative to those sleeping ≥7 hours. TL was positively correlated with HPI (r = 0.195; p = 0.009). ApoE-ε4 allele carriers who slept for less than 7 hours had shortest TL (p = 0.01) compared to non-carriers. Plasma sRAGE level was significantly (p = 0.001) lower in individuals who sleep &lt;7 hours and ApoE-ϵ4 carriers. Our results suggest that inadequate sleep duration or poor HPI is associated with shorter TL in cognitively normal elderly people and that carriage of APOE-ε4 genotype may influence the extent of these effects.

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma

The levels of different classes of extracellular RNAs (exRNAs) remain stable in bodily fluids. The detection of either enriched or depleted specific subsets of salivary microRNAs (miRNAs) has the potential to serve as a non-invasive approach for biomarker development. Thus, salivary miRNAs have emerged as a promising molecular tool for early diagnosis and screening of oral squamous cell carcinoma (OSCC). Total RNA was extracted from saliva supernatant of 33 OSCC patients and 12 controls (discovery set), and the differential expression of 8 cancer-related miRNAs was detected by TaqMan assay. Among the screened miRNAs, miR-30c-5p (p < 0.04) was significantly decreased in OSCC saliva. The same transcriptional behavior of miR30c-5p was observed in an additional validation set. miR-30c-5p showed a significant statistical difference between cases and controls with areas under the curve (AUC) of 0.82 (95% CI: 0.71–0.89). The sensitivity and the specificity of miR-30c-5p were 86% and 74%, respectively. The target identification analysis revealed enrichment of miR-30c-5p targets in p53 and Wnt signaling pathways in OSCC. Additionally, the miR-30c-5p targets had clinical significance related to overall survival. In conclusion, these findings show that downregulated miR-30c-5p has the potential to serve as a novel, non-invasive biomarker for early OSCC detection.