• PLA2G7 gene
• coronary artery atherosclerotic heart disease
• lipid profile
• serum Lp-PLA2

• Medical and Health Science and Technology in 2021 from The Inner Mongolia Autonomous Region
• Scientific research project of Hohhot First Hospital
• Hohhot Medical and Health Science and Technology Program
• Inner Mongolia Talent Development Fund

• lp-pla2
• pla2g7
• r92h
• rs1805017
• single nucleotide polymorphism
• ​coronary artery disease
• ​​​​​​atherosclerosis

The study evaluated the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) gene polymorphisms and coronary heart disease (CHD), in order to explore the molecular genetics of CHD.

Groups of CHD patients (n = 283) and healthy controls (n = 261) were involved in this study. R92H, V279F, and A379V polymorphisms of LP-PLA2 gene were confirmed using polymerase chain reaction (PCR) and direct DNA sequencing. These polymorphisms and their interaction were also analyzed as potential risk factors of CHD.

In this study population, the genotypes of R92H (GG, GA, and AA), V279F (CC, AC, and AA) and A379V (GG, GA, and AA) were studied. There was a significantly difference in frequencies of R92H between CHD patients and controls (P < 0.05). In contrast, no significant difference in frequencies of V279F and A379V existed between CHD patients and controls. Furthermore, R92H and A379V were in strong linkage disequilibrium.

These results suggested that R92H polymorphism might contribute to increased risk of CHD.

Ischemic coronary heart disease (IHD) is the leading cause of death worldwide. Genetic variation is presumed to be a major factor underlying sex differences for IHD events, including mortality. The purpose of this study was to identify sex-specific candidate genes associated with all-cause mortality among people diagnosed with coronary artery disease (CAD).

We performed a sex-stratified, exploratory genome-wide association (GWAS) screen using existing data from CAD-diagnosed males (n = 510) and females (n = 174) who reported European ancestry from the Duke Catheterization Genetics biorepository. Extant genotype data for 785,945 autosomal SNPs generated with the Human Omni1-Quad BeadChip (Illumina, CA, USA) were analyzed using an additive inheritance model. We estimated instantaneous risk of all-cause mortality by genotype groups across the 11-year follow-up using Cox multivariate regression, covarying for age and genomic ancestry.

The top GWAS hits associated with all-cause mortality among people with CAD included 8 SNPs among males and 15 among females (p = 1 × 10⁻⁶ or 10⁻⁷), adjusted for covariates. Cross-sex comparisons revealed distinct candidate genes. Biologically relevant candidates included rs9932462 (EMP2/TEKT5) and rs2835913 (KCNJ6) among males and rs7217169 (RAP1GAP2), rs8021816 (PRKD1), rs8133010 (PDE9A), and rs12145981 (LPGAT1) among females.

We report 20 sex-specific candidate genes having suggestive association with all-cause mortality among CAD-diagnosed subjects. Findings demonstrate proof of principle for identifying sex-associated genetic factors that may help explain differential mortality risk in people with CAD. Replication and meta-analyses in larger studies with more diverse samples will strengthen future work in this area.

• Breast cancer
• Cardiovascular disease
• DNA methylation
• Epigenetics
• Radiation

• Cardiovascular Diseases/genetics
• DNA Methylation
• Epigenesis, Genetic
• Humans
• Neoplasm Recurrence, Local/genetics
• Radiation, Ionizing

T-lymphoblastic lymphoma (T-LBL), a neoplasm of immature T-cell precursors or lymphoblasts, is a clinically aggressive disease. In general, patients with T-LBL have a poor prognosis and often have high-risk clinical features, such as mediastinal masses, central nervous system infiltration, or other indications of high tumor burden; however, extensive thrombi are not common.

A 27-year-old woman presented to the Department of General Surgery with cervical lymph node enlargement accompanied by cough, wheezing, and palpitation for 3 mo. A complete blood count showed a white blood cell count of 1.6 × 10⁹/L, a hemoglobin concentration of 135 g/L, and a platelet count of 175 × 10⁹/L. A biopsy sample of the lymph node mass indicated T-cell lymphoblastic lymphoma, and the bone marrow immunophenotype indicated early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Abdominal and chest enhanced computed tomography showed thrombi in the superior vena cava, inferior vena cava, right hepatic vein, azygos vein, and right atrium. The ultrasonic cardiogram showed a thrombus in the right atrium of 5.23 cm × 4.21 cm. The patient was first treated with low-dose dexamethasone and low-molecular-weight heparin followed by 2 cycles of chemotherapy. Then, the ultrasonic cardiogram showed that thrombus in the right atrium had disappeared and the patient had achieved complete cytological remission. The maintenance therapy of the patient included chidamide 30 mg/wk, and she survived for 6 mo.

The incidence of venous thromboembolism is high in lymphoma; however, extensive thrombi with heart thrombosis is rare. Chemotherapy is the major method of treatment for lymphoma with thrombosis. We successfully treated a patient with T-LBL complicated by extensive thrombi, including a large right atrial thrombus, with combined chemotherapy containing liposomal doxorubicin, and the patient achieved complete remission. Maintenance therapy with chidamide was also effective.

• T-lymphoblastic lymphoma
• Thrombus
• Cardiac thrombosis
• Chemotherapy
• Case report

• age-related disease
• candidate gene analyses
• coronary artery disease
• genome-wide association study
• survival analysis

Coronary artery disease (CAD) is an age-associated condition that greatly increases the risk of mortality. The purpose of this study was to identify gene variants associated with all-cause mortality among individuals with clinically phenotyped CAD using a genome-wide screening approach.

We performed discovery (n = 684), replication (n = 1,088), and meta-analyses (N = 1,503) for association of genomic variants with survival outcome using secondary data from White participants with CAD from two GWAS sub-studies of the Duke Catheterization Genetics Biorepository. We modeled time from catheterization to death or last follow-up (median 7.1 years, max 12 years) using Cox multivariable regression analysis. Target statistical screening thresholds were p × 10^–8 for the discovery phase and Bonferroni-calculated p-values for the replication (p < 5.3 × 10^–4) and meta-analysis (p < 1.6 × 10^–3) phases. Genome-wide analysis of 785,945 autosomal SNPs revealed two SNPs (rs13007553 and rs587936) that had the same direction of effect across all three phases of the analysis, with suggestive p-value association in discovery and replication and significant meta-analysis association in models adjusted for clinical covariates. The rs13007553 SNP variant, LINC01250, which resides between MYTIL and EIPR1, conferred increased risk for all-cause mortality even after controlling for clinical covariates [HR 1.47, 95% CI 1.17–1.86, p(adj) = 1.07 × 10^–3 (discovery), p(adj) = 0.03 (replication), p(adj) = 9.53 × 10^–5 (meta-analysis)]. MYT1L is involved in neuronal differentiation. TSSC1 is involved in endosomal recycling and is implicated in breast cancer. The rs587936 variant annotated to DAB2IP was associated with increased survival time [HR 0.65, 95% CI 0.51–0.83, p(adj) = 4.79 × 10^–4 (discovery), p(adj) = 0.02 (replication), p(adj) = 2.25 × 10^–5 (meta-analysis)]. DAB2IP is a ras/GAP tumor suppressor gene which is highly expressed in vascular tissue. DAB2IP has multiple lines of evidence for protection against atherosclerosis.

Replicated findings identified two candidate genes for further study regarding association with survival in high-risk CAD patients: novel loci LINC01250 (rs13007553) and biologically relevant candidate DAB2IP (rs587936). These candidates did not overlap with validated longevity candidate genes. Future research could further define the role of common variants in survival outcomes for people with CAD and, ultimately, improve longitudinal outcomes for these patients.

• age-related disease
• candidate gene analyses
• coronary artery disease
• genome-wide association study
• survival analysis

• Hepatocellular carcinoma
• Metabolic
• Prognostic
• Signature

• Oxylipin
• RNASeq
• lipids
• liquid chromatography tandem-mass spectrometry
• pain

Phospholipases A2 (PLA₂s) belong to a superfamily of enzymes responsible for hydrolysis of the sn-2 fatty acids of membrane phospholipids to release arachidonic acid. PLA₂s are the rate limiting enzyme for the downstream synthesis of prostaglandins and leukotrienes that are the main mediators of inflammation. The extracellular forms of this enzyme are also called the secretary phospholipase A2 (sPLA₂) and are distributed extensively in most of the tissues in the human body. Their integral role in inflammatory pathways has been the primary reason for the extensive research on this molecule. The catalytic mechanism of sPLA₂ is initiated by a histidine/aspartic acid/calcium complex within the active site. Though they are known to have certain housekeeping functions, certain mutations of sPLA₂ are known to be implicated in causation of certain pathologies leading to diseases such as atherosclerosis, cardiovascular diseases, benign fleck retina, neurodegeneration, and asthma. We present an overview of human sPLA₂ and a comprehensive compilation of the mutations that result in various disease phenotypes. The study not only helps to have a holistic understanding of human sPLA₂ mutations and their clinical implications, but is also a useful platform to initiate research pertaining to structure–function relationship of the mutations to develop effective therapies for management of these diseases.

• clinical implications
• mutations
• sPLA2
• secretary phospholipase A2
• structure–function relationship

• Lp-PLA2
• carotid plaque
• gene polymorphism
• genetic

• Kawasaki disease
• PLA2G7
• immunoglobulin therapy
• polymorphism
• rs1051931

• Baltic cod
• Contracaecum osculatum
• Growth
• Immunity
• Liver
• Metabolism

• Animals
• Fish Diseases/immunology
• Fish Diseases/parasitology
• Gadus morhua/growth & development
• Gene Expression Profiling/veterinary
• Larva/growth & development
• Larva/physiology
• Liver/metabolism
• Liver/parasitology
• Rhabditida/growth & development
• Rhabditida/physiology
• Rhabditida Infections/immunology
• Rhabditida Infections/parasitology
• Rhabditida Infections/veterinary
• Transcriptome/immunology

• fragment-based lead discovery
• inflammation
• inhibitors
• lipoprotein-associated phospholipase A2
• vascular diseases

• Q281R mutation
• atherosclerosis
• complex human diseases
• lipoprotein-associated phospholipase A2
• non-synonymous single nucleotide polymorphism
• pharmacogenomics

The KIF6 rs20455 polymorphism has been verified as an important genetic factor of coronary heart disease (CHD), but with controversial results. The aim of this study was to explore the association between KIF6 rs20455 polymorphism and susceptibility to CHD.

All eligible studies were identified by searching Medline (mainly PubMed), EMBASE, the Web of Science, Cochrane Collaboration Database, Chinese National Knowledge Infrastructure, Wanfang Database and China Biological Medicine up to October 5, 2016.Odds ratios (ORs) with 95% confidence interval (CI) were used to explore the association between KIF6 rs20455 polymorphism and CHD risk. Begg’s and Egger’s tests were used to examine the publication bias. Subgroup analysis and sensitivity analysis were performed to test the reliability and stability of the results. All the analyses were carried out by Stata 12.0 software.

A total of 28 publications including 50 individual studies were analyzed in this present work. There are no significant association found between KIF6 rs20455 polymorphism and CHD risk (Homozygote model: OR = 1.007, 95% CI =0.952–1.066, P = 0.801; Heterozygote model: OR = 1.009, 95% CI = 0.968–1.052, P = 0.636; Dominant model: OR = 1.007, 95% CI = 0.966–1.048, P = 0.753; Recessive model: OR = 0.989, 95% CI = 0.943–1.037, P = 0.655; Allele comparison model: OR = 1.00, 95% CI = 0.971–1.030, P = 0.988). Furthermore, subgroup analyses were performed by ethnicity, source of control.

Our result suggests that KIF6 rs20455 polymorphism may not be associated with CHD susceptibility. However, additional very well-designed large-scale studies are warranted to confirm our results.

• Coronary heart disease
• KIF6 rs20455
• Meta-analysis
• Polymorphism

• Lipoprotein-associated phospolipase A2 (Lp-PLA2)
• PLA2G7
• atherosclerosis
• single-nucleotide polymorphisms (SNPs)

• Animals
• Gene Regulatory Networks
• Male
• Mice
• Myocardium/metabolism
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• Oxidative Stress
• Signal Transduction
• Transcriptome

• R01 HL118067 NHLBI NIH HHS
• R03 AG042860 NIA NIH HHS
• T32 HL007918 NHLBI NIH HHS

Blunt snout bream (Megalobrama amblycephala) is a widely favored herbivorous fish species and is a frequentlyused fish model for studying the metabolism physiology. This study aimed to provide a comprehensive illustration of the mechanisms of a high-starch diet (HSD) induced lipid metabolic disorder by identifying microRNAs (miRNAs) controlled pathways in glucose and lipid metabolism in fish using high-throughput sequencing technologies. Small RNA libraries derived from intestines, livers, and brains of HSD and normal-starch diet (NSD) treated M. amblycephala were sequenced and 79, 124 and 77 differentially expressed miRNAs (DEMs) in intestines, livers, and brains of HSD treated fish were identified, respectively. Bioinformatics analyses showed that these DEMs targeted hundreds of predicted genes were enriched into metabolic pathways and biosynthetic processes, including peroxisome proliferator-activated receptor (PPAR), glycolysis/gluconeogenesis, and insulin signaling pathway. These analyses confirmed that miRNAs play crucial roles in glucose and lipid metabolism related to high wheat starch treatment. These results provide information on further investigation of a DEM-related mechanism dysregulated by a high carbohydrate diet.

• Megalobrama amblycephala
• glucose and lipid metabolism
• microRNAs
• wheat starch

• Animals
• Cyprinidae/genetics
• Cyprinidae/metabolism
• Fish Proteins/genetics
• Fish Proteins/metabolism
• Gene Expression Profiling/methods
• Gene Library
• Gene Ontology
• Glucose/metabolism
• Glycolysis/genetics
• High-Throughput Nucleotide Sequencing/methods
• Lipid Metabolism/genetics
• MicroRNAs/genetics
• Protein Interaction Maps/genetics

• Arthritis, Rheumatoid
• Asthma
• Comorbidity
• Epidemiology
• Genetic Heterogeneity
• Phenotype
• Risk

• R01 HL126667 NHLBI NIH HHS
• R21 AI116839 NIAID NIH HHS
• National Institutes of Health
• Sanford Foundation

The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women.

A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006–2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed.

No significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women.

There were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 → H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.

• Enzyme activity
• Gene polymorphism
• Oxidative stress
• PAF acetylhydrolase
• Polycystic ovary syndrome

• 17-β-Estradiol
• Coronary heart disease
• DNA methylation
• PLA2G7

• metabolomics
• phenotypes
• prognosis

Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs—rs1462845 and rs6788787—using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01–1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69–0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08–1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05–1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects on survival. Additional analyses demonstrated that the homozygous risk genotype (‘A/A’) fully explained the increased hazard in both cohorts. None of the post-hoc analyses in control subjects were significant for any model. This suggests that genetic effects of rs1462845 on survival are unique to CAD presence. This represents formal, replicated evidence of genetic contribution of rs1462845 to increased risk for all-cause mortality; the contribution is unique to CAD case status and specific to males with severe burden of CAD.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Comorbidity
• Coronary Artery Disease/diagnosis
• Coronary Artery Disease/epidemiology
• Coronary Artery Disease/etiology
• Coronary Artery Disease/mortality
• Female
• Follow-Up Studies
• Genetic Variation
• Genotype
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Proportional Hazards Models
• Risk Factors
• Severity of Illness Index
• Sex Factors
• Survival Analysis
• Young Adult

• K99 NR011054 NINR NIH HHS
• P30 AG028716 NIA NIH HHS
• R00 NR011054 NINR NIH HHS
• T32 AG000029 NIA NIH HHS
• National Institute on Aging
• National Institute of Nursing Research
• Duke University School of Nursing
• Duke University John A. Hartford Center for Excellence
• Duke OIAC Pepper Center

• Asthma
• Epidemiology
• Inflammation
• Myocardial infarction
• Risk factors
• Systemic

• Atherosclerosis
• Coronary artery disease
• Genetics
• Genome-wide association study
• Heritability
• In-stent restenosis
• Myocardial infarction

• T32 HL083828 NHLBI NIH HHS

• ischemic stroke
• platelet-activating factor acetylhydrolase
• polymorphisms

Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the Lp-PLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.

• Lipoprotein-associated phospholipase A2
• Atherosclerosis
• Coronary artery disease
• Myocardial infarction
• Prognosis

• Cardiovascular disease
• KIF6
• Meta-analysis
• Systematic review
• Trp719Arg polymorphism

• Air pollution
• Biomarkers
• Biorepository
• Cardiometabolic disease
• Cardiovascular disease
• Genetics
• Genomics
• Geocoding
• Metabolomics

• central obesity, CVD risk gene, EBF1, gene-by-stress interaction
• chronic psychosocial stress

• allergy
• corticotropin-releasing hormone
• heart
• inflammation
• interleukin 6
• mast cell
• stress
• urocortin

• Animals
• Cell Degranulation
• Coronary Artery Disease/immunology
• Coronary Artery Disease/psychology
• Coronary Vessels/immunology
• Corticotropin-Releasing Hormone/metabolism
• Cytokines/metabolism
• Humans
• Inflammation Mediators/metabolism
• Mast Cells/immunology
• Stress, Psychological/immunology

• R01 AR047652 NIAMS NIH HHS
• R01 NS066205 NINDS NIH HHS
• R01 NS071361 NINDS NIH HHS

• Ischemic stroke
• Lp-PLA2
• PLA2G7
• Polymorphisms

• Atherosclerosis/genetics
• Atherosclerosis/pathology
• Cell Movement/genetics
• Cell Proliferation
• Cells, Cultured
• Cellular Senescence/genetics
• Collagen/genetics
• DNA Methylation/genetics
• Epigenesis, Genetic
• Gene Expression Regulation
• Humans
• Myocytes, Smooth Muscle/cytology
• Myocytes, Smooth Muscle/metabolism
• Neointima/genetics

• K99/R00HL089412 NHLBI NIH HHS
• HL73042 NHLBI NIH HHS
• R01 HL073389 NHLBI NIH HHS
• AG028716 NIA NIH HHS
• P30 AG028716 NIA NIH HHS
• HL073389 NHLBI NIH HHS
• R00 HL089412 NHLBI NIH HHS
• P01 HL073042 NHLBI NIH HHS

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time =  5.3 years, interquartile range  = 3.3–8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR)  = 1.47, 95% confidence interval (CI)  = 1.17, 1.84, p  = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR  = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.

• Cardiovascular Diseases/diagnosis
• Cardiovascular Diseases/genetics
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Polymorphism, Genetic
• Receptor, Serotonin, 5-HT2C/genetics
• Risk Factors

• P01 HL036587 NHLBI NIH HHS
• R01 HL095987 NHLBI NIH HHS
• HL095987 NHLBI NIH HHS

Survivorship is a trait characterized by endurance and virility in the face of hardship. It is largely considered a psychosocial attribute developed during fatal conditions, rather than a biological trait for robustness in the context of complex, age-dependent diseases like coronary artery disease (CAD). The purpose of this paper is to present the novel phenotype, survivorship in CAD as an observed survival advantage concurrent with clinically significant CAD. We present a model for characterizing survivorship in CAD and its relationships with overlapping time- and clinically-related phenotypes. We offer an optimal measurement interval for investigating survivorship in CAD. We hypothesize genetic contributions to this construct and review the literature for evidence of genetic contribution to overlapping phenotypes in support of our hypothesis. We also present preliminary evidence of genetic effects on survival in people with clinically significant CAD from a primary case-control study of symptomatic coronary disease. Identifying gene variants that confer improved survival in the context of clinically appreciable CAD may improve our understanding of cardioprotective mechanisms acting at the gene level and potentially impact patients clinically in the future. Further, characterizing other survival-variant genetic effects may improve signal-to-noise ratio in detecting gene associations for CAD.

• LSAMP gene
• atherosclerosis
• cardioprotection
• coronary artery disease
• novel phenotype
• survival
• survivorship

Previous genome-wide association studies (GWAS) have revealed seven single nucleotide polymorphisms (SNPs) that affect lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity or levels in American and European individuals. A total of 290 coronary heart disease (CHD) patients, 198 non-CHD patients and 331 unrelated healthy volunteers were recruited for the present case-control study of Han Chinese. Four SNPs (rs964184 of ZNF259, rs7528419 of CELSR2 and rs7756935 and rs1805017 of PLA2G7) were shown to be significantly associated with CHD. The rs964184-G allele of the ZNF259 gene was identified as a risk factor of CHD in females (odds ratio (OR) =1.49, 95% confidence interval (CI) =1.00–2.22, P=0.05). The rs7528419-G allele of the CELSR2 gene was protective against CHD in males (OR=0.48, 95% CI=0.25–0.93, P=0.04). The other two alleles (rs7756935-C and rs1805017-A) of the PLA2G7 gene acted as protective factors against CHD in females (rs7756935-C: OR=0.59, 95% CI=0.35–1.00, P=0.05; rs1805017-A: OR=0.51, 95% CI=0.28–0.93, P=0.03). Moreover, rs1805017 of the PLA2G7 gene was associated with the severity of CHD only in females (r²=0.02, P=0.04). We identified four Lp-PLA₂-associated SNPs significantly associated with CHD in a Han Chinese population. Specifically, rs7528419 was protective factor against CHD in males, while the other two SNPs (rs7756935 and rs1805017 of the PLA2G7 gene) were protective factors against CHD in females and rs964184 of the ZNF259 gene was regarded as a risk factor for CHD in females.

• CELSR2
• PLA2G7
• ZNF259
• coronary heart disease
• lipoprotein-associated phospholipase A
• single nucleotide polymorphism

There is strong but mostly circumstantial evidence that genetic factors modulate the severity of influenza infection in humans. Using genetically diverse but fully inbred strains of mice it has been shown that host sequence variants have a strong influence on the severity of influenza A disease progression. In particular, C57BL/6J, the most widely used mouse strain in biomedical research, is comparatively resistant. In contrast, DBA/2J is highly susceptible.

To map regions of the genome responsible for differences in influenza susceptibility, we infected a family of 53 BXD-type lines derived from a cross between C57BL/6J and DBA/2J strains with influenza A virus (PR8, H1N1). We monitored body weight, survival, and mean time to death for 13 days after infection. Qivr5 (quantitative trait for influenza virus resistance on chromosome 5) was the largest and most significant QTL for weight loss. The effect of Qivr5 was detectable on day 2 post infection, but was most pronounced on days 5 and 6. Survival rate mapped to Qivr5, but additionally revealed a second significant locus on chromosome 19 (Qivr19). Analysis of mean time to death affirmed both Qivr5 and Qivr19. In addition, we observed several regions of the genome with suggestive linkage. There are potentially complex combinatorial interactions of the parental alleles among loci. Analysis of multiple gene expression data sets and sequence variants in these strains highlights about 30 strong candidate genes across all loci that may control influenza A susceptibility and resistance.

We have mapped influenza susceptibility loci to chromosomes 2, 5, 16, 17, and 19. Body weight and survival loci have a time-dependent profile that presumably reflects the temporal dynamic of the response to infection. We highlight candidate genes in the respective intervals and review their possible biological function during infection.