Risk of coronary artery disease in celiac disease population.
Ontology highlight
ABSTRACT:
SUBMITTER: Gajulapalli RD
PROVIDER: S-EPMC5539680 | biostudies-other | 2017 Jul-Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Recent genome-wide association studies have identified PHACTR1 as a critical risk gene associated with polyvascular diseases. However, it remains elusive how PHACTR1 is involved in endothelial dysfunction. Here, we show that PHACTR1 triggers endothelial inflammation by activating NF-κB and disrupts Nitric oxide production by inhibiting Akt/eNOS activation to induce endothelial diastolic disorder. Whereas, Atorvastatin particularly plays an inhibitory effect on PHACTR1 gene expression in a dose-dependent manner among PHACTR family in endothelial cells. PHACTR1 may interact with PP1 with coupling with heat shock protein 8 (HSPA8) to dephosphorylate Akt or eNOS.
2022-08-16 | PXD034213 | Pride
Project description:The objective of this study was to assess the prevalence of risk factors for coronary artery disease (CAD) in government employees across India.The study population consisted of government employees in different parts of India ({n=10,642 men and n=1966 women; age 20-60 years}) and comprised various ethnic groups living in different environmental conditions. Recruitment was carried out in 20 cities across 14 states, and in one union territory. All selected individuals were subjected to a detailed questionnaire, medical examinations and anthropometric measurements. Blood samples were collected for blood glucose and serum lipid profile estimation, and resting ECG was recorded. Results were analysed using appropriate statistical tools.The study revealed that 4.6% of the study population had a family history of premature CAD. The overall prevalence of diabetes was 16% (5.6% diagnosed during the study and the remaining 10.4% already on medication). Hypertension was present in 21% of subjects. The prevalence of dyslipidemia was significantly high, with 45.6% of study subjects having a high total cholesterol/high density lipoprotein ratio. Overall, 78.6% subjects had two or more risk factors for CAD.The present study demonstrates a high prevalence of CAD risk factors in the Indian urban population. Therefore, there is an immediate need to initiate measures to raise awareness of these risk factors so that individuals at high risk for future CAD can be managed.
| S-EPMC4281543 | biostudies-other
Project description:Background and objectivesThe objective of this study was to analyze and compare risk factors for peripheral artery disease (PAD) and coronary artery disease (CAD).Subjects and methodsThe sample included 7936 Korean patients aged ≥20 years who were hospitalized from 1994 to 2004. Of the 7936 subjects, PAD (n=415), CAD (n=3686), and normal controls (Control) (n=3835) were examined at the Health Promotion Center, Samsung Medical Center.ResultsThe mean age (years) of PAD subjects was 64.4 (±9.3), while CAD subjects was 61.2 (±9.9), and Control subjects was 59.9 (±9.1) (p<0.01). The proportion of males was 90.6% for PAD, 71.4% for CAD, and 75.5% for Control subjects (p<0.01). The adjusted odds ratios (ORs) for hypertension, diabetes mellitus, hypercholesterolemia, smoking, metabolic syndrome and chronic kidney disease were significantly higher in subjects with PAD or CAD compared to those in Control. However, the ORs for high density lipoprotein, being overweight, and being obese were significantly lower in PAD subjects compared to those in Control.ConclusionWe found that cardiovascular risk factors were in fact risk factors for both PAD and CAD.
| S-EPMC3675306 | biostudies-literature
Project description:Smooth muscle cells (SMCs) go through pehnotypic transition during atherosclerosis progression. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of SMCs in aorta tissuee.
2023-02-03 | GSE214423 | GEO
Project description:BackgroundEpidemiological studies have repeatedly observed a markedly higher risk for coronary artery disease (CAD) in Scotland as compared to England. Up to now, it is unclear whether environmental or genetic factors might explain this phenomenon.MethodsUsing UK Biobank (UKB) data, we assessed CAD risk, based on the Framingham risk score (FRS) and common genetic variants, to explore the respective contribution to CAD prevalence in Scotland (n = 31,963) and England (n = 317,889). We calculated FRS based on sex, age, body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), antihypertensive medication, smoking status, and diabetes. We determined the allele frequency of published genome-wide significant risk CAD alleles and a weighted genetic risk score (wGRS) for quantifying genetic CAD risk.ResultsPrevalence of CAD was 16% higher in Scotland as compared to England (8.98% vs. 7.68%, P < 0.001). However, the FRS only predicted a marginally higher CAD risk (less than 1%) in Scotland (12.5 ± 10.5 vs.12.6 ± 10.6, P = 0.03). Likewise, the overall number of genome-wide significant variants affecting CAD risk (157.6 ± 7.7 and 157.5 ± 7.7; P = 0.12) and a wGRS for CAD (2.49 ± 0.25 in both populations, P = 0.14) were remarkably similar in the English and Scottish population. Interestingly, we observed substantial differences in the allele frequencies of individual risk variants. Of the previously described 163 genome-wide significant variants studied here, 35 variants had higher frequencies in Scotland, whereas 37 had higher frequencies in England (P < 0.001 each).ConclusionsNeither the traditional risk factors included in the FRS nor a genetic risk score (GRS) based on established common risk alleles explained the higher CAD prevalence in Scotland. However, we observed marked differences in the distribution of individual risk alleles, which emphasizes that even geographically and ethnically closely related populations may display relevant differences in the genetic architecture of a common disease.
| S-EPMC8650538 | biostudies-literature
Project description:ObjectiveCoronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single-nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD.MethodsCoronary artery calcification (CAC) as detected by computed tomography was used as a measure of CAD in 561 patients with RA. One hundred SNPs associated with CAD in the general population were genotyped or imputed, and their relationship to CAC was established through multiple regression analysis for individual SNPs and a genetic risk score representing their cumulative effect.ResultsNinety-one CAD-related SNPs were genotyped successfully; of these, 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively, in the genetic risk score. Only rs579459 (ABO) and rs17676451 (HAL) had a consistent positive association between genotype and CAC, with a significant increase in the frequency of the effect allele in both homozygous and heterozygous genotype distributions. Five were variably negatively associated. Furthermore, a positive association between the Disease Activity Score in 28 joints and CAC was observed, and after adjustment for traditional cardiovascular risk factors, it was not modified by correcting for the CAD-related SNP genetic risk score.ConclusionThe increased risk of CAC in patients with RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population.
| S-EPMC5553209 | biostudies-literature
Project description:BACKGROUND:Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk. METHODS:We derived polygenic risk scores (PRSs) with ?6M variants separately for LDL-C and TG with weights from a UK Biobank-based genome-wide association study with ?324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen). RESULTS:In FINRISK, median LDL-C was 3.39 (95% CI, 3.38-3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82-2.94) to 3.78 (95% CI, 3.71-3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18-1.20) mmol/L, ranging from 0.97 (95% CI, 0.94-1.00) to 1.55 (95% CI, 1.48-1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was 1.36 (95% CI, 1.24-1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19-1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16-1.38] for LDL-C and 1.24 [95% CI, 1.13-1.36] for TG PRS). CONCLUSIONS:The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.
| S-EPMC7176338 | biostudies-literature
Project description:BackgroundGenome-wide association studies have identified multiple loci associated with coronary artery disease and myocardial infarction, but only a few of these loci are current targets for on-market medications. To identify drugs suitable for repurposing and their targets, we created 2 unique pipelines integrating public data on 49 coronary artery disease/myocardial infarction-genome-wide association studies loci, drug-gene interactions, side effects, and chemical interactions.MethodsWe first used publicly available genome-wide association studies results on all phenotypes to predict relevant side effects, identified drug-gene interactions, and prioritized candidates for repurposing among existing drugs. Second, we prioritized gene product targets by calculating a druggability score to estimate how accessible pockets of coronary artery disease/myocardial infarction-associated gene products are, then used again the genome-wide association studies results to predict side effects, excluded loci with widespread cross-tissue expression to avoid housekeeping and genes involved in vital processes and accordingly ranked the remaining gene products.ResultsThese pipelines ultimately led to 3 suggestions for drug repurposing: pentolinium, adenosine triphosphate, and riociguat (to target CHRNB4, ACSS2, and GUCY1A3, respectively); and 3 proteins for drug development: LMOD1 (leiomodin 1), HIP1 (huntingtin-interacting protein 1), and PPP2R3A (protein phosphatase 2, regulatory subunit b-double prime, α). Most current therapies for coronary artery disease/myocardial infarction treatment were also rediscovered.ConclusionsIntegration of genomic and pharmacological data may prove beneficial for drug repurposing and development, as evidence from our pipelines suggests.
| S-EPMC6205215 | biostudies-literature
Project description:Recently, a significant epigenetic component in the pathogenesis of Coronary Artery Disease (CAD) has been realized. Here, we evaluated the possible association of candidate Single Nucleotide Polymorphisms (SNPs) in the epigenetic-regulatory gene, DNA methyltransferase 1 (DNMT1), with CAD in Chinese Han population. Five tag SNPs (rs16999593, rs2336691, rs2228611, rs4804494, rs7253062) were analyzed by High Resolution Melt (HRM) method in 476 CAD patients and 478 controls. Overall, there were significant differences in the genotype and allele distributions of rs2228611 and rs2336691, between patients and controls. The minor A allele of rs2228611 was associated with a lower risk of CAD (p = 0.034); modest effect in the additive analysis but also marginal significance was found in the recessive model [ORadditive = 0.404 (0.184, 0.884), p = 0.023 and ORrecessive = 0.452 (0.213, 0.963), p = 0.040] after adjusting for confounders. While the rs2336691 A allele were associated with a higher risk of developing CAD (p = 0.037); borderline significant association in both additive and dominant models [ORadditive = 1.632 (1.030, 2.583), p = 0.037 and ORdominant = 1.599 (1.020, 2.507), p = 0.040]. In conclusion, these data provide the first evidence that occurrence of CAD may be moderated by genetic variation in the gene involved in the epigenetic machinery.
| S-EPMC4284731 | biostudies-literature
Project description:BackgroundSurgical methods such as coronary artery bypass grafting and percutaneous coronary interventions (PCI) are widely used along with traditional conservative therapy in the treatment of coronary artery disease. The disease outcome directly depends on timely diagnosis and treatment. A significant role in predicting the effectiveness of treatment is given to personification of treatment and management of the patient. In this case, the determining component is its individual genetic status.MethodsThe study groups included persons of Kazakh nationality which identify themselves, their biological parents, and biological grandparents on the maternal and paternal side as Kazakh. Research groups included 108 people at the age from 45 to 65 years of both sexes. Blood samples genotyping was carried out by PCR using highly specific TaqMan samples. Thermo Fisher cloud application was used for genotypes determining on the base of an automatic algorithm.ResultsThe article presents the results of the evaluation of gene polymorphisms associated with coronary artery restenosis in a population of Kazakh nationality. 3 SNPs were determined when searching for an association with stenting due to coronary artery thrombosis: rs7543130 (p=0.009324), rs6785930 (p=0.016858), rs7819412 (p=0.061325).ConclusionFour polymorphisms associated with the risk of developing coronary heart disease were revealed during the study of polymorphisms among the people of the Kazakh population. Three SNPs were determined when searching for an association with stenting due to coronary artery thrombosis. It should be noted that the Bonferonni correction for multiple comparisons did not reveal significant polymorphisms associated with coronary artery disease, which requires further research with more quantity of samples.
| S-EPMC10201125 | biostudies-literature