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Aminoacyl-tRNA synthetases (ARSs) are widely found in organisms, which can activate amino acids and make them bind to tRNA through ester bond to form the corresponding aminoyl-tRNA. The classic function of ARS is to provide raw materials for protein biosynthesis. Recently, emerging evidence demonstrates that ARSs play critical roles in controlling inflammation, immune responses, and tumorigenesis as well as other important physiological and pathological processes. With the recent development of genome and exon sequencing technology, as well as the discovery of new clinical cases, ARSs have been reported to be closely associated with a variety of cardiovascular diseases (CVDs), particularly angiogenesis and cardiomyopathy. Intriguingly, aminoacylation was newly identified and reported to modify substrate proteins, thereby regulating protein activity and functions. Sensing the availability of intracellular amino acids is closely related to the regulation of a variety of cell physiology. In this review, we summarize the research progress on the mechanism of CVDs caused by abnormal ARS function and introduce the clinical phenotypes and characteristics of CVDs related to ARS dysfunction. We also highlight the potential roles of aminoacylation in CVDs. Finally, we discuss some of the limitations and challenges of present research. The current findings suggest the significant roles of ARSs involved in the progress of CVDs, which present the potential clinical values as novel diagnostic and therapeutic targets in CVD treatment., Graphical abstract, Zou et al. reviewed the functional roles of aminoacyl-tRNA synthetases (ARSs) in cardiovascular diseases (CVDs) and discussed the involved molecular mechanisms. These reviews provide important insights into the potential value of ARS and provide potential diagnosis biomarker or therapeutic targets for CVDs, especially for angiogenesis and cardiomyopathy.

Background: ADAM 10 & 17, the two most well-known members of disintegrin and metalloproteinases (ADAMs), are responsible for the cleavage of diverse transmembrane proteins into bioactive molecules in the renal tubular cells. Objective: The purpose of this study is to understand the effects of ADAM 10 & 17 double-knockout (DKO) on renal and vascular functions using the renal tubular cell-specific ADAM 10 & 17 DKO mice. Results: We tested the renal and vascular functions in three groups (n=10-15 per group) of male and female wild-type (WT), vehicle, and DKO mice. The urine output ( P < 0.05) and glomerular filtration rate ( P < 0.01) of DKO mice were significantly lower than those of WT and vehicle control groups. The urinary sodium ( P < 0.0001) and potassium ( P < 0.01) excretion in DKO mice were also significantly reduced. Consistently, we found a significant decrease in urea ( P < 0.0001) and creatinine ( P < 0.0001) clearance in DKO mice, suggesting that the renal function is impaired when both ADAM 10 & 17 are depleted. In addition, the pulse wave velocity ( P < 0.0001), and blood pressure including systolic blood pressure ( P -value < 0.0001), diastolic blood pressure ( P < 0.0001), and mean blood pressure ( P < 0.0001) levels of DKO mice were significantly higher than those of WT and vehicle controls, indicating that ADAM 10 & 17 depletion impairs renal and vascular functions and causes hypertension. This phenomenon is further supported by the evidence that DKO mice showed a slower relaxation response to acetylcholine, compared to WTs. Next, to understand the changes in proteomic profiles in DKO kidneys, we performed proteomic analysis of WT and DKO kidney tissues and identified ~100 differentially expressed proteins (DEPs). These DEPs are highly enriched in drug metabolism, metabolic pathways, and TGF-beta signaling, PPAR-signaling and AGE-RAGE signaling pathways, suggesting that ADAM 10 & 17 may play a role in renal cellular metabolism, cell growth, differentiation, and apoptosis. Conclusions: The depletion of ADAM 10 & 17 impairs the renal and vascular functions likely via disrupting the cellular metabolism and homeostasis.

Atherosclerosis (AS) is a leading cause of cardiovascular diseases (CVDs) and it results in a high rate of death worldwide, with an increased prevalence with age despite advances in lifestyle management and drug therapy. Atherosclerosis is a chronic progressive inflammatory process, and it mainly presents with lipid accumulation, foam cell proliferation, inflammatory response, atherosclerotic plaque formation and rupture, thrombosis, and vascular calcification. Therefore, there is a great need for reliable therapeutic drugs or remedies to cure or alleviate atherosclerosis and reduce the societal burden. Ginsenosides are natural steroid glycosides and triterpene saponins obtained mainly from the plant ginseng. Several recent studies have reported that ginsenosides have a variety of pharmacological activities against several diseases including inflammation, cancer and cardiovascular diseases. This review focuses on describing the different pharmacological functions and underlying mechanisms of various active ginsenosides (Rb1,-Rd, -F, -Rg1, -Rg2, and -Rg3, and compound K) for atherosclerosis, which could provide useful insights for developing novel and effective anti-cardiovascular drugs.

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5' end and 2'-O-methylation at the 3' end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentially regulate various diseases. Specifically, concomitant with the development of next-generation sequencing techniques, piRNAs have been found to be differentially expressed in CVDs, indicating their potential involvement in the occurrence and progression of heart diseases. However, the molecular mechanisms and signaling pathways involved with piRNA function have not been fully elucidated. In this review, we present the current understanding of the piRNAs from the perspectives of biogenesis, characteristics, biological function, and regulatory mechanisms, and highlight their potential roles and underlying mechanisms in CVDs, which will provide new insights into the potential applications of piRNAs in the clinical diagnosis, prognosis, and therapeutic strategies for heart diseases.

Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.

Accumulation of reactive oxygen species is a common phenomenon in cardiac stress conditions, for instance, coronary artery disease, aging-related cardiovascular abnormalities, and exposure to cardiac stressors such as hydrogen peroxide (H2O2). Mitochondrial protein 18 (Mtp18) is a novel mitochondrial inner membrane protein, shown to involve in the regulation of mitochondrial dynamics. Although Mtp18 is abundant in cardiac muscles, its role in cardiac apoptosis remains elusive. The present study aimed to detect the role of Mtp18 in H2O2-induced mitochondrial fission and apoptosis in cardiomyocytes. We studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. We then analyzed mitochondrial morphological dynamics with MitoTracker Red staining; apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) and cell death detection assays; and protein expression with immunoblotting. Here, we observed that Mtp18 could regulate oxidative stress- mediated mitochondrial fission and apoptosis in cardiac myocytes. Mechanistically, we found that Mtp8 induced mitochondrial fission and apoptosis by enhancing dynamin-related protein 1 (Drp1) accumulation. Conversely, knockdown of Mtp18 interfered with Drp1-associated mitochondrial fission and subsequent activation of apoptosis in both HL-1 cells and primary cardiomyocytes. However, overexpression of Mtp18 alone was not sufficient to execute apoptosis when Drp1 was minimally expressed, suggesting that Mtp18 and Drp1 are interdependent in apoptotic cascade. Together, these data highlight the role of Mtp18 in cardiac apoptosis and provide a novel therapeutic insight to minimize cardiomyocyte loss via targetting mitochondrial dynamics.

Excessive production of free radicals can induce cellular damage, which is associated with many diseases. RNA is more susceptible to oxidative damage than DNA due to its single-stranded structure, and lack of protective proteins. Yet, oxidative damage to RNAs received little attention. Accumulating evidence reveals that oxidized RNAs may be dysfunctional and play fundamental role in the occurrence and development of type 2 diabetes (T2D) and its complications. Oxidized guanine nucleoside, 8-oxo-7, 8-dihydroguanine (8-oxoGuo) is a biomarker of RNA oxidation that could be associated with prognosis in patients with T2D. Nowadays, some clinical trials used antioxidants for the treatment of T2D, though the pharmacological effects remained unclear. In this review, we overview the cellular handling mechanisms and the consequences of the oxidative RNA damage for the better understanding of pathogenesis of T2D and may provide new insights to better therapeutic strategy.

Smoking is an independent risk factor for atherosclerosis. The smoke produced by tobacco burning contains more than 7000 chemicals, among which nicotine is closely related to the occurrence and development of atherosclerosis. Nicotine, a selective cholinergic agonist, accelerates the formation of atherosclerosis by stimulating nicotinic acetylcholine receptors (nAChRs) located in neuronal and non-neuronal tissues. This review introduces the pathogenesis of atherosclerosis and the mechanisms involving nicotine and its receptors. Herein, we focus on the various roles of nicotine in atherosclerosis, such as upregulation of growth factors, inflammation, and the dysfunction of endothelial cells, vascular smooth muscle cells (VSMC) as well as macrophages. In addition, nicotine can stimulate the generation of reactive oxygen species, cause abnormal lipid metabolism, and activate immune cells leading to the onset and progression of atherosclerosis. Exosomes, are currently a research hotspot, due to their important connections with macrophages and the VSMC, and may represent a novel application into future preventive treatment to promote the prevention of smoking-related atherosclerosis. In this review, we will elaborate on the regulatory mechanism of nicotine on atherosclerosis, as well as the effects of interference with nicotine receptors and the use of exosomes to prevent atherosclerosis development.

tsRNAs are small fragments of RNAs with specific lengths that are generated by particular ribonucleases, such as dicer and angiogenin (ANG), clipping on the rings of transfer RNAs (tRNAs) in specific cells and tissues under specific conditions. Depending on where the splicing site is, tsRNAs can be segmented into two main types, tRNA‐derived stress‐induced RNAs (tiRNAs) and tRNA‐derived fragments (tRFs). Many studies have shown that tsRNAs are functional molecules, not the random degradative products of tRNAs. Notably, due to their regulatory mechanism in regulating mRNA stability, transcription, ribosomal RNA (rRNA) synthesis and RNA reverse transcription, tsRNAs are significantly involved in the cell function, such as cell proliferation, migration, cycle and apoptosis, as well as the occurrence and development of a variety of diseases. In addition, tsRNAs may represent a new generation of clinical biomarkers or therapeutic targets because of their stable structures, high conservation and widely distribution, particularly in the peripheral tissues, bodily fluids and exosomes. In this review, we describe the generation, function and mechanism of tsRNAs and illustrate the current research progress of tsRNAs in various diseases, highlight their potentials as biomarkers and therapeutic targets in clinical application. Although our understanding of tsRNAs is still in infancy, the application prospects shown in this field deserve further exploration., tsRNAs are generated under stress condition which are functional molecules. Due to their regulatory mechanism in regulating mRNA stability, transcription, ribosomal RNA (rRNA) synthesis and RNA reverse transcription, tsRNAs are significantly involved in the cellular function, including cell proliferation, migration, cell cycle and apoptosis, as well as the occurrence and development of a variety of diseases.

Aim This study aimed to assess the overall status of burnout in nurses in China on a national scale and investigate the demographic characteristics related to burnout and the relationships between demographics, job satisfaction and burnout. Methods This was a national cross-sectional study conducted by the Chinese Nursing Association between July 2016 and July 2017. Data were collected using a structured, self-administered questionnaire. Results A total of 51 406 registered nurses in 311 Chinese cities completed the questionnaire. Fifty per cent of the participants suffered burnout, and 33.8% of nurses had high scores on emotional exhaustion, 66.6% had high scores on depersonalization and 93.5% had low scores on personal accomplishment; 16.2% reported a high level of job satisfaction, only 0.4% was satisfied with their jobs and 70.7% intended to leave their jobs. Marital status, educational level, income and years of working experience affected job burnout. Nurses with a high level of burnout were more likely to have a high degree of job dissatisfaction and intend to leave their jobs. Conclusion We found a high prevalence of burnout among nurses in China. Nursing managers need to pay more attention to job burnout and its influencing factors. Interventions to reduce nurse burnout should be implemented.

Introduction: With the rapid development of sequencing technologies, several long non-coding RNAs (lncRNAs) have been identified; among which many are significant players in cardiac physiology and pathology. Doxorubicin (Dox), a commonly used anticancer agent, in the long-term can induce cardiotoxicity, limiting its clinical use. Despite the multiple signaling pathways involved in Dox cardiotoxicity, most of them ultimately lead to the activation of apoptosis, contributing to the progressive cardiomyocyte loss, and hence ensuring heart failure. Methods and Results: Microarray analysis showed that multiple lncRNAs were differentially expressed between control and doxorubicin-treated groups, denoting that lncRNAs may play a critical role in Dox cardiotoxicity. Functional enrichment analysis displayed that the differentially expressed genes are annotated to MAPK signaling and cardiac hypertrophic pathways. CMDL-1 is first characterized in rat cardiomyocytes and is the most significantly downregulated lncRNA after doxorubicin exposure. CMDL-1 is located upstream to the transient receptor potential cation channel, subfamily M, member 7 (Trpm-7), which can function as a kinase by phosphorylating itself or other substrates. Mechanistic analysis indicated that lentiviral overexpression of CMDL-1 decreased Dox-induced mitochondrial fission (MitoTracker Red CMXRos) and apoptosis (TUNEL and flow cytometry) in cardiomyocytes. Bioinformatic and experimental data showed that CMDL-1 could bind to Drp1. Overexpression of CMDL-1 promoted its association with Drp1, as well as with phosphorylated (p)-Drp1, evidenced by RNA immunoprecipitation analysis. However, overexpression of CMDL-1 couldn’t effectively reduce mitochondrial fission if Drp1 was minimally expressed by siDrp1. These findings suggest that CMDL-1 could prevent mitochondrial fission and apoptosis by impairing Drp1 phosphorylation. Conclusions: Collectively, we demonstrated that a novel lncRNA CMDL-1 could play a protective role in cardiac injury and could be a potential therapeutic target in Dox cardiotoxicity. Our study is additional evidence of the less appreciated mechanism of lncRNAs, modulating the phosphorylation status of its interacting proteins.

The use of circulating microRNAs as biomarkers opens up new opportunities for the diagnosis of cardiovascular diseases because of their specific expression profiles. The aim of the present study was to identify circulating microRNAs in human plasma as potential biomarkers of heart failure and related diseases. We used real-time quantitative PCR to screen microRNA in plasma samples from 62 normal controls and 62 heart failure samples. We found that circulating miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 expressed differently between healthy controls and heart failure patients. Plasma levels of miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 were unaffected by hemolysis. Correlation analysis showed any two of these miRNAs possess a strong correlation, indicating a possibility of combined analysis. MiR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 could be combined in two or three or more combinations. The results suggest that miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 may be a new diagnostic biomarker for heart failure and related diseases.

The long‐term usage of doxorubicin (DOX) is largely limited due to the development of severe cardiomyopathy. Many studies indicate that DOX‐induced cardiac injury is related to reactive oxygen species generation and ultimate activation of apoptosis. The role of novel mitochondrial fission protein 1 (Mtfp1) in DOX‐induced cardiotoxicity remains elusive. Here, we report the pro‐mitochondrial fission and pro‐apoptotic roles of Mtfp1 in DOX‐induced cardiotoxicity. DOX up‐regulates the Mtfp1 expression in HL‐1 cardiac myocytes. Knockdown of Mtfp1 prevents cardiac myocyte from undergoing mitochondrial fission, and subsequently reduces the DOX‐induced apoptosis by preventing dynamin 1‐like (Dnm1l) accumulation in mitochondria. In contrast, when Mtfp1 is overexpressed, a suboptimal dose of DOX can induce a significant percentage of cells to undergo mitochondrial fission and apoptosis. These data suggest that knocking down of Mtfp1 can minimize the cardiomyocytes loss in DOX‐induced cardiotoxicity. Thus, the regulation of Mtfp1 expression could be a novel therapeutic approach in chemotherapy‐induced cardiotoxicity.

One of the severe limitations of chemotherapy is the development of drug resistance. However, the mechanisms underlying chemotherapy resistance remain to be elucidated. Mitochondrial mediated apoptosis is a form of cell death induced by chemotherapy. Several chemotherapeutic agents have been shown to induce mitochondrial fission, and finally activate the apoptosis cascade in various cancer cells. Here, we report that the mitochondrial membrane protein 18 (MTP18) induced mitochondrial fragmentation in gastric cancer cells under doxorubicin (DOX) exposure. Upon over-expression of MTP18, a sub-cytotoxic dose of DOX could sensitize a significant number of cells to undergo mitochondrial fission and subsequent apoptosis. These findings suggest that MTP18 can enhance the sensitivity of gastric cancer cells to DOX. Mechanistically, we found that MTP18 enriched dynamic-related protein 1 (DRP1) accumulation in mitochondria and it was responsible for mediating DOX-induced signaling required for mitochondrial fission. Intriguingly, MTP18 expression was downregulated during DOX treatment. Thus, down-regulation of MTP18 expression could be one of the resistance factors interfering with DOX-induced apoptosis in gastric cancer cells.

Doxorubicin (DOX) as a chemotherapeutic drug is widely used to treat a variety of human tumors. However, a major factor limiting its clinical use is its cardiotoxicity. The molecular components and detailed mechanisms regulating DOX-induced cardiotoxicity remain largely unidentified. Here we report that Foxo3a is downregulated in the cardiomyocyte and mouse heart in response to DOX treatment. Foxo3a attenuates DOX-induced mitochondrial fission and apoptosis in cardiomyocytes. Cardiac specific Foxo3a transgenic mice show reduced mitochondrial fission, apoptosis and cardiotoxicity upon DOX administration. Furthermore, Foxo3a directly targets mitochondrial dynamics protein of 49kDa (MIEF2) and suppresses its expression at transcriptional level. Knockdown of MIEF2 reduces DOX-induced mitochondrial fission and apoptosis in cardiomyocytes and in vivo. Also, knockdown of MIEF2 protects heart from DOX-induced cardiotoxicity. Our study identifies a novel pathway composed of Foxo3a and MIEF2 that mediates DOX cardiotoxicity. This discovery provides a promising therapeutic strategy for the treatment of cancer therapy and cardioprotection.

The accumulation of unrepaired oxidatively damaged DNA can influence both the rate of ageing and life expectancy of an organism. Mapping oxidative DNA damage sites at whole-genome scale will help us to recognize the damage-prone sequence and genomic feature information, which is fundamental for ageing research. Here, we developed an algorithm to map the whole-genome oxidative DNA damage at single-base resolution using Single-Molecule Real-Time (SMRT) sequencing technology. We sequenced the genomic oxidative DNA damage landscape of C. elegans at different age periods to decipher the potential impact of genomic DNA oxidation on physiological ageing. We observed an age-specific pattern of oxidative modification in terms of motifs, chromosomal distribution, and genomic features. Integrating with RNA-Seq data, we demonstrated that oxidative modification in promoter regions was negatively associated with the expression of pro-longevity genes, denoting that oxidative modification in pro-longevity genes may exert epigenetic potential and thus affect lifespan determination. Together, our study opens up a new field for exploration of “oxigenetics,” that focuses on the mechanisms of redox-mediated ageing.SummaryWe developed an algorithm to map the oxidative DNA damage at single-base resolution.Oxidative DNA damage landscape in C. elegans illustrated an age-specific pattern in terms of motifs, chromosomal distribution, and genomic features.Oxidative modification in older worms occurred higher frequency at the sex chromosome, with the preference for promoter and exon regions.Oxidative modification in promoter regions of pro-longevity genes was negatively associated with their expression, suggesting the oxidative-driven transcript reprogramming of pro-longevity genes in physiological ageing.

Apoptosis repressor with caspase recruitment domain (ARC) is a potent inhibitor of apoptosis. Under physiological conditions, ARC is abundantly expressed in terminally differentiated cells, including cardiomyocytes, skeletal muscles and neurons. ARC serves a key role in determining cell fate, and abnormal ARC expression has been demonstrated to be associated with abnormal cell growth. Previous studies have revealed that ARC was upregulated in several different types of solid tumor, where it suppressed tumor cell apoptosis. Furthermore, the increased expression levels of ARC in cancer cells contributed to the development of therapeutic resistance and adverse clinical outcomes in patients with leukemia. However, the exact role of ARC, as well as the underlying molecular mechanisms involved, remain poorly understood. The present review summarizes the characteristics of ARC and its cytoprotective role under different conditions and describes the potential ARC as a new target for cancer therapy.

Cardiovascular disease (CVD) is one of the most threatening diseases to human health and life, and the number of patients is increasing year by year. Thus, it is of great significance to study the pathogenesis, prevention and treatment of CVDs. The occurrence and development of CVDs involve dynamic, complex and delicate intracellular processes and the pathogenesis is not entirely clear. In contrast to genetic mutations, most of the protein post-translational modifications (PTMs) are reversible, and can affect the activity, stability, subcellular localization, protein-protein interaction etc., of the substrate targets, emerging as key mediators of a number of CVD progression. Under pathological conditions, the PTMs undergo aberrant balances which cause changes of the substrate target proteins in expression level, localization and capacity to activate downstream signaling pathways. Therefore, new approaches can be created aiming to correct the abnormal PTM alterations in treating CVDs. This review summarizes some of the more recent advances in PTMs, focusing on SUMOylation, neddylation, succinylation, and prenylation, and the effect of these modifications on cardiovascular function and progression, which may provide potential targets for future therapeutics.

Apoptosis plays a critical role in the development of myocardial infarction. Cardiomyocytes are enriched with mitochondria and excessive mitochondrial fission can trigger cellular apoptosis. Recently, the mitochondrial ubiquitin ligase (MITOL), localized in the mitochondrial outer membrane, was reported to play an important role in the regulation of mitochondrial dynamics and apoptosis. However, the underlying mechanism of its action remains uncertain. The present study was aimed at uncovering the role of MITOL in the regulation of cardiomyocyte apoptosis. Our results showed that MITOL expression was up‐regulated in cardiomyocytes in response to apoptotic stimulation. Mitochondrial ubiquitin ligase overexpression blocked dynamin‐related protein 1 accumulation in the mitochondria, and attenuated the mitochondrial fission induced by hydrogen peroxide. Conversely, MITOL knockdown sensitized cardiomyocytes to undergo mitochondrial fission, resulting in subsequent apoptosis. These findings suggest that MITOL plays a protective role against apoptosis in cardiomyocytes, and may serve as a potential therapeutic target for apoptosis‐related cardiac diseases.

In the history of nucleic acid research, DNA has always been the main research focus. After the sketch of the human genome was completed in 2000, RNA has been started to gain more attention due to its abundancies in the cell and its essential role in cellular physiology and pathologies. Recent studies have shown that RNAs are susceptible to oxidative damage and oxidized RNA is able to break the RNA strand, and affect the protein synthesis, which can lead to cell degradation and cell death. Studies have shown that RNA oxidation is one of the early events in the formation and development of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. However, its molecular mechanism, as well as its impact on these diseases, are still unclear. In this article, we review the different types of RNA oxidative damage and the neurodegenerative diseases that are reported to be associated with RNA oxidative damage. In addition, we discuss recent findings on the association between RNA oxidative damage and the development of neurodegenerative diseases, which will have great significance for the development of novel strategies for the prevention and treatment of these diseases.

This study aimed to detect the interactions of several single nucleotide polymorphisms (SNPs) and alcohol consumption on blood pressure levels. Genotypes of 10 SNPs in the ATP-binding cassette transporter A1 (ABCA-1), acyl-CoA:cholesterol acyltransferase-1 (ACAT-1), low density lipoprotein receptor (LDLR), hepatic lipase gene (LIPC), endothelial lipase gene (LIPG), methylenetetrahydrofolate reductase (MTHFR), the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP), proprotein convertase subtilisin-like kexin type 9 (PCSK9), peroxisome proliferator-activated receptor delta (PPARD), and Scavenger receptor class B type 1 (SCARB1) genes were determined in 616 nondrinkers and 608 drinkers. The genotypic frequencies of LDLR rs5925, LIPC rs2070895, MTHFR rs1801133, and MYLIP rs3757354 SNPs were significantly different between nondrinkers and drinkers. The levels of systolic blood pressure (ABCA-1 rs2066715 and rs2070895), diastolic blood pressure (rs2070895), and pulse pressure (PP) (rs2066715, ACAT-1 rs1044925, and rs1801133) in nondrinkers, and systolic blood pressure (rs1044925 and SCARB1 rs5888), diastolic blood pressure (rs1044925 and LIPG rs2000813), and PP (PCSK9 rs505151 and rs5888) in drinkers were different among the genotypes (P

Background The overall quantitative estimate on the possible association of adiponectin concentrations with mortality in patients with cardiovascular diseases (CVD) has not been reported. Methods We performed a systematic review and meta-analysis of prospective studies to evaluate the overall quantitative estimates on the adiponectin levels for risk of mortality in patients with CVD. MEDLINE, EMBASE, CINAHL, and the Cochrane Library (up to Mar 22, 2014) were used to search for studies evaluating the effect of adiponectin levels on mortality in patients with CVD. Random-effect models were selected to estimate overall effect estimates. Results Data from 14063 CVD patients enrolled in 15 prospective cohort and 1 nested case control studies were collated. The meta-analyses showed strong positive association of adiponectin with all-cause (n = 14 studies, overall pooled effect estimate = 1.45 [95% CI, 1.17–1.79]) and cardiovascular (n = 11 studies, overall pooled effect estimate = 1.69 [1.35–2.10]) mortality, for the highest tertile of adiponectin levels versus the lowest tertile. Subgroup analyses show study characteristics (including effect estimate, mean age, study location, sample sizes, gender, durations of follow-up, types of primary event, and acute or chronic CVD) did not substantially influence these positive associations. Conclusions Our results showed that increased baseline plasma adiponectin levels are significantly associated with elevated risk of all-cause and cardiovascular mortality in subjects with CVD. These positive associations may have been amplified by adjustment for potential intermediates or residual confounding, and their basis requires further investigation.

The single nucleotide polymorphisms (SNPs) in the BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) genes have been associated with one or more serum lipid traits in the European populations. However, little is known about such association in the Chinese populations. Our objectives were to determine the association of the BUD13/ZNF259 SNPs and their haplotypes with hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG) and to identify the possible gene–gene interactions among these SNPs. Genotyping of 6 SNPs was performed in 634 hyperlipidaemic and 547 normolipidaemic participants. The ZNF259 rs2075290, ZNF259 rs964184 and BUD13 rs10790162 SNPs were significantly associated with serum lipid levels in both HCH and non-HCH populations (P < 0.008–0.001). On single locus analysis, only BUD13 rs10790162 was associated with HCH (OR: 2.23, 95% CI: 1.05, 4.75, P = 0.015). The G-G-A-A-C-C haplotype, carrying rs964184-G-allele, was associated with increased risk of HCH (OR: 1.35, 95% CI: 1.10, 1.66, P = 0.005) and HTG (OR: 1.75, 95% CI: 1.39, 2.21, P = 0.000). The A-C-G-G-C-C and A-C-A-G-T-C haplotypes, carrying rs964184-C-allele, were associated with reduced risk of HCH (OR: 0.77, 95% CI: 0.61, 0.99, P = 0.039 and OR: 0.66, 95% CI: 0.47, 0.94, P = 0.021 respectively). On multifactor dimensionality reduction analyses, the two- to three-locus models showed a significant association with HCH and HTG (P < 0.01–0.001). The BUD13/ZNF259 SNPs, which were significant in the European populations, are also replicable in the Southern Chinese population. Moreover, inter-locus interactions may exist among these SNPs. However, further functional studies are required to clarify how these SNPs and genes actually affect the serum lipid levels.

The association between the phosphodiesterase 3A (PDE3A) rs7134375 single nucleotide polymorphism (SNP) and serum lipid levels are not well understood in the general population. The present study was performed in order to detect the association between the rs7134375 SNP and serum lipid levels in the Guangxi Mulao and Han populations. The genotypes of the PDE3A rs7134375 SNP in 761 subjects of the Mulao population and 774 subjects of the Han Chinese population were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. It was observed that serum low-density lipoprotein cholesterol and apolipoprotein B levels were higher in the Mulao population than in the Han population (P

Backgroud: Both alcohol consumption and the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene polymorphism modulate serum lipid levels, but their interactions on serum lipid profiles are still unknown. The present study was undertaken to detect the interactions of PCSK9 E670G polymorphism and alcohol consumption on serum lipid levels. Methods: Genotypes of the PCSK9 E670G in 1352 unrelated subjects (785 non-drinkers and 567 drinkers) were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions between PCSK9 E670G genotypes and alcohol consumption on serum lipid parameters were detected by using a factorial design covariance analysis after controlling for potential confounders. Results: The levels of serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in non-drinkers (P < 0.01 for all), whereas the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoB were lower in drinkers than in non-drinkers (P < 0.001 for all). The genotypic and allelic frequencies of PCSK9 E670G were not different between non-drinkers and drinkers (P > 0.05 for each). The subjects with AA genotype in non-drinkers had higher serum LDL-C levels than the subjects with AG genotype, whereas the subjects with AG genotype in drinkers had higher serum TC levels than the subjects with AA genotypes (P < 0.05 for each). The effects of alcohol consumption on TC and LDL-C levels depended upon genotypes, the subjects with AA genotype had lower serum TC and LDL-C levels in drinkers than in non-drinkers. Conclusions: Alcohol consumption can modify the effects of the PCSK9 E670G polymorphism on serum TC and LDL-C levels. The subjects with AA genotype of the PCSK9 E670G benefit more from alcohol consumption than the subjects with AG genotype in decreasing serum TC and LDL-C levels.

The association of rs707921 and rs707922 SNPs in the apolipoprotein M (APOM) gene and serum lipid levels is still controversial. This study aimed to detect the association of the APOM rs707921 and rs707922 SNPs and several environmental factors with serum lipid profiles. Genotyping of rs707921 and rs707922 was performed in 703 of Mulao’s and 707 of Han’s participants. The serum levels of TG in Mulao, and TG and HDL-C in Han were different between the A and C allele carriers of rs707921 (P

Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) −250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01–0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity.

The interactions of single nucleotide polymorphisms (SNPs) and cigarette smoking on blood pressure levels are limited. The present study was undertaken to detect nine lipid-related SNPs and their interactions with cigarette smoking on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaⅡ, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 935 nonsmokers and 845 smokers. The interactions were detected by factorial regression analysis. The frequencies of genotypes (ACAT-1 and LIPG), alleles (ABCA-1), and both genotypes and alleles (LDL-R, LIPC, PPARD and SCARB1) were different between nonsmokers and smokers (P < 0.05-0.001). The levels of pulse pressure (PP, ABCA-1), and systolic, diastolic blood pressure (SBP, DBP) and PP (LIPC) in nonsmokers were different among the genotypes (P < 0.01-0.001). The levels of SBP (ABCA-1, ACAT-1, LIPG and PCSK9), DBP (ACAT-1, LDL-R, LIPC, PCSK9 and PPARD), and PP (LIPC, LIPG, MTHFR and PCSK9) in smokers were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1, ACAT-1 and PCSK9; ACAT-1, LDL-R, MTHFR and PCSK9; and ABCA-1, LIPC, PCSK9 and PPARD were shown interactions with cigarette smoking to influence SBP, DBP and PP levels (P < 0.05-0.001); respectively. The differences in blood pressure levels between the nonsmokers and smokers might partly result from different interactions of several SNPs and cigarette smoking.

Backgroud: The associations of scavenger receptor class B type 1 (SCARB1) rs5888 single nucleotide polymorphism (SNP) and serum lipid levels are inconsistant among diverse ethnic populations. The present study was undertaken to detect the association of rs5888 SNP and serum lipid levels in the Guangxi Mulao and Han populations. Methods: Genotypes of the SCARB1 rs5888 SNP in 801 subjects of Mulao and 807 subjects of Han Chinese were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results: Serum apolipoprotein (Apo) B levels and the T allelic frequency were higher in Mulao than in Han. Serum high-density lipoprotein cholesterol (HDL-C) levels in Mulao were different among the genotypes, the subjects with TT genotype had lower HDL-C levels than the subjects with CC or CT genotype in female (P < 0.05). For the Han population, serum triglyceride (TG), HDL-C, ApoAI, ApoB levels and the ratio of ApoAI to ApoB in males were different among the genotypes, the T allele carriers had lower serum HDL-C, ApoAI levels and ApoAI/ApoB ratio and higher serum ApoB levels than the T allele noncarriers (P < 0.05 for all), the subjects with TT genotype had higher serum TG levels than the subjects with CC or CT genotype. Serum HDL-C levels in Mulao females and serum HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males were correlated with genotypes by the multiple linear regression analysis. Serum lipid parameters were also influenced by genotype-environmental interactions in Han but not in Mulao populations. Conclusions: These results suggest that the rs5888 SNP is associated with serum HDL-C levels in Mulao females, and TG, HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males. The differences in serum ApoB levels between the two ethnic groups might partially attribute to different SCARB1 genotype-environmental interactions.

Backgroud: The associations of scavenger receptor class B type 1 (SCARB1) rs5888 single nucleotide polymorphism (SNP) and serum lipid levels are inconsistant among diverse ethnic populations. The present study was undertaken to detect the association of rs5888 SNP and serum lipid levels in the Guangxi Mulao and Han populations.Methods: Genotypes of the SCARB1 rs5888 SNP in 801 subjects of Mulao and 807 subjects of Han Chinese were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.Results: Serum apolipoprotein (Apo) B levels and the T allelic frequency were higher in Mulao than in Han. Serum high-density lipoprotein cholesterol (HDL-C) levels in Mulao were different among the genotypes, the subjects with TT genotype had lower HDL-C levels than the subjects with CC or CT genotype in female (P < 0.05). For the Han population, serum triglyceride (TG), HDL-C, ApoAI, ApoB levels and the ratio of ApoAI to ApoB in males were different among the genotypes, the T allele carriers had lower serum HDL-C, ApoAI levels and ApoAI/ApoB ratio and higher serum ApoB levels than the T allele noncarriers (P < 0.05 for all), the subjects with TT genotype had higher serum TG levels than the subjects with CC or CT genotype. Serum HDL-C levels in Mulao females and serum HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males were correlated with genotypes by the multiple linear regression analysis. Serum lipid parameters were also influenced by genotype-environmental interactions in Han but not in Mulao populations.Conclusions: These results suggest that the rs5888 SNP is associated with serum HDL-C levels in Mulao females, and TG, HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males. The differences in serum ApoB levels between the two ethnic groups might partially attribute to different SCARB1 genotype-environmental interactions.

Both endothelial lipase gene (LIPG) 584CT (rs2000813) polymorphism and alcohol consumption modulate serum lipid levels. But their interactions on serum lipid profiles are not well known. The present study was undertaken to detect the interactions of LIPG 584CT polymorphism and alcohol consumption on serum lipid levels. Genotyping of the LIPG 584CT was performed in 763 unrelated nondrinkers and 520 drinkers aged 15-85 years. The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI, and the ratio of ApoAI to ApoB were higher in drinkers than in nondrinkers (P.01 for all). There were no significant differences in the genotypic and allelic frequencies between nondrinkers and drinkers. The levels of TC, HDL-C, and ApoAI in nondrinkers were different among the three genotypes (P.05-.01), the subjects with CT genotype had higher TC, HDL-C, and ApoAI levels than the subjects with CC genotype. The levels of HDL-C and ApoAI in drinkers were different among the three genotypes (P.001 and P.05; respectively), the individuals with TT genotype had higher HDL-C and ApoAI levels than the individuals with CT and CC genotypes. The interactions between LIPG 584CT genotypes and alcohol consumption on serum HDL-C (P.01) and ApoAI levels (P.05) were also detected by using a factorial regression analysis after controlling for potential confounders. The levels of TC in nondrinkers were correlated with LIPG 584CT alleles (P.05), whereas the levels of TG and HDL-C were associated with LIPG 584CT alleles (P.05) and genotypes (P.05), respectively. These results suggest that the subjects with TT genotype benefit more from alcohol consumption than the subjects with CT and CC genotypes in increasing serum HDL-C and ApoAI levels.

This study aimed to detect the interactions of several single nucleotide polymorphisms (SNPs) and alcohol consumption on blood pressure levels. Genotypes of 10 SNPs in the ATP-binding cassette transporter A1 (ABCA-1), acyl-CoA:cholesterol acyltransferase-1 (ACAT-1), low density lipoprotein receptor (LDLR), hepatic lipase gene (LIPC), endothelial lipase gene (LIPG), methylenetetrahydrofolate reductase (MTHFR), the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP), proprotein convertase subtilisin-like kexin type 9 (PCSK9), peroxisome proliferator-activated receptor delta (PPARD), and Scavenger receptor class B type 1 (SCARB1) genes were determined in 616 nondrinkers and 608 drinkers. The genotypic frequencies of LDLR rs5925, LIPC rs2070895, MTHFR rs1801133, and MYLIP rs3757354 SNPs were significantly different between nondrinkers and drinkers. The levels of systolic blood pressure (ABCA-1 rs2066715 and rs2070895), diastolic blood pressure (rs2070895), and pulse pressure (PP) (rs2066715, ACAT-1 rs1044925, and rs1801133) in nondrinkers, and systolic blood pressure (rs1044925 and SCARB1 rs5888), diastolic blood pressure (rs1044925 and LIPG rs2000813), and PP (PCSK9 rs505151 and rs5888) in drinkers were different among the genotypes (P 0.005-0.001). The interactions of several SNPs and alcohol consumption on systolic blood pressure (rs2066715, rs1044925, rs5925, rs2070895, rs1801133, rs3757354, PPARD rs2016520, and rs5888), diastolic blood pressure (rs2066715, rs1044925, rs5925, rs2000813, rs3757354, and rs2016520), and PP (rs1044925, rs2070895, rs1801133, rs3757354, rs505151, and rs5888) were observed (P 0.005-0.001). The differences in blood pressure levels between the nondrinkers and drinkers might be partially attributed to the interactions of these SNPs and alcohol consumption.

This study aimed to detect the association between the MLX interacting protein-like (MLXIPL), BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese Mulao and Han populations. Genotyping of 9 SNPs was performed in 825 Mulao and 781 Han participants. The genotype and allele frequencies of ZNF259 rs2075290 and rs964184, and BUD13 rs10790162 SNPs were different between the Mulao and Han populations (P < 0.001). The SNPs of ZNF259 rs2075290 and BUD13 rs10790162 were associated with serum total cholesterol levels; ZNF259 rs2075290 and rs964184, BUD13 rs10790162, and MLXIPL rs3812316 and rs13235543 were associated with triglyceride (TG); and MLXIPL rs35332062 was associated with apolipoprotein (Apo) A1 in the Mulaos (P < 0.006–0.001). However, in the Hans, the SNPs of ZNF259 rs2075290 and BUD13 rs10790162 were associated with serum TG levels; ZNF259 rs2075290 was associated with low-density lipoprotein cholesterol and the ApoA1/ApoB ratio (P < 0.006–0.001). Significant linkage disequilibria were noted among ZNF259 rs2075290 and rs964184 and BUD13 rs10790162, and between MLXIPL rs3812316 and rs13235543 (r2 > 0.05, P < 0.001). The haplotypes of A-C-G-A-C (rs2075290A-rs964184C-rs10790162G-rs17119975A-rs11556024C) and C-C-C-C (rs799161C-rs35332062C-rs3812316C-rs13235543C) accounted for over half of the % haplotype of each ethnic group.

Background: Little is known about the association of ZNF259 rs2075290 single nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population. This study aimed to detect the association of ZNF259 rs2075290 SNP and environmental factors with serum lipid levels between males and females in the Mulao and Han populations. Methods and Results: Genotyping of ZNF259 rs2075290 SNP was performed in 788 of Mulao and 778 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequencies were significantly different between Mulao and Han populations (AA, 50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P = 0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05-0.01) but not in Mulao's. Conclusions: The subjects with AG/GG genotype in Mulao males and females and Han females have less favorable lipid profiles than those with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have more favorable lipid profiles than those with AA genotype. These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity.

Background The rs17145738 single nucleotide polymorphism (SNP) near MLX interacting protein-like/transducin (beta)-like 2 (MLXIPL/TBL2) loci is associated with serum lipid levels, but the results are inconsistent in diverse ethnic/racial groups. The current study was to investigate the association of MLXIPL/TBL2 rs17145738 SNP and several environmental factors with serum lipid profiles in the Guangxi Mulao and Han populations. Methods A total of 649 subjects of Mulao nationality and 712 participants of Han nationality aged 16–84 years were randomly selected from our previous stratified randomized samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.001). There were no significant differences in the genotypic and allelic frequencies of the MLXIPL/TBL2 rs17145738 SNP between the two ethnic groups or between males and females. The T allele carriers had higher triglyceride (TG) and ApoB levels in Mulao, and higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in Han than the T allele non-carriers (P < 0.05 for all). Subgroup analyses showed that the T allele carriers had higher ApoB levels in both Mulao and Han females than the T allele non-carriers, but the T allele carriers had lower ApoB levels in Han males than the T allele non-carriers (P < 0.05, respectively). The T allele carriers in Han had higher TC, high-density lipoprotein cholesterol (HDL-C) levels and ApoA1/ApoB ratio and lower TG levels in males, and higher LDL-C levels and lower ApoA1/ApoB ratio in females than the T allele non-carriers (P < 0.05 for all). Serum TC levels in the combined population of the two ethnic groups and in Han, and HDL-C levels in Han males were correlated with genotypes (P < 0.05 for all). Serum lipid parameters were also correlated with several environmental factors (P < 0.05-0.01). Conclusions The association of MLXIPL/TBL2 rs17145738 SNP and serum lipid profiles is different between the Mulao and Han populations. There is a sex-specific association in the both ethnic groups.

Background: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS). Methods: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism. Results: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each). Conclusions: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.