Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project.

ABSTRACT:

Background

Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals.

Methods

We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR).

Results

Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters.

Conclusions

Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis.

SUBMITTER: Zamarron-Licona E

PROVIDER: S-EPMC8145882 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

<i>FOXA3</i> Polymorphisms Are Associated with Metabolic Parameters in Individuals with Subclinical Atherosclerosis and Healthy Controls-The GEA Mexican Study.

Project description:FOXA3 is a transcription factor involved in the macrophage cholesterol efflux and macrophage reverse cholesterol transport reducing the atherosclerotic lesions. Thus, the present study aimed to establish if the FOXA3 polymorphisms are associated with subclinical atherosclerosis (SA) and cardiometabolic parameters. Two FOXA3 polymorphisms (rs10410870 and rs10412574) were determined in 386 individuals with SA and 1070 controls. No association with SA was observed. The rs10410870 polymorphism was associated with a low risk of having total cholesterol >200 mg/dL, non-HDL-cholesterol > 160 mg/dL, and a high risk of having LDL pattern B and insulin resistance adipose tissue in individuals with SA, and with a high risk of having interleukin 10 <p25 and magnesium deficiency in controls. The rs10412574 polymorphism was associated with a low risk of insulin resistance of the adipose tissue and a high risk of aspartate aminotransferase >p75 in individuals with SA, and with a low risk of LDL pattern B and a high risk of a magnesium deficiency in controls. Independent analysis in 846 individuals showed that the rs10410870 polymorphism was associated with a high risk of aortic valve calcification. In summary, FOXA3 polymorphisms were not associated with SA; however, they were associated with cardiometabolic parameters in individuals with and without SA.

| S-EPMC9139129 | biostudies-literature

<i>MRE11A</i> Polymorphisms Are Associated With Subclinical Atherosclerosis and Cardiovascular Risk Factors. A Case-Control Study of the GEA Mexican Project.

Project description:DNA damage and subsequent repair pathways have been involved in the initiation and progression of atherosclerosis. Meiotic recombination 11 homolog A (MRE11A) gene polymorphisms have been associated with the presence of myocardial infarction. We analyzed five MRE11A gene polymorphisms in 386 individuals with subclinical atherosclerosis and 1093 healthy controls. Under different models, the rs13447720 (Odds ratio = 0.646, Padditive = 0.009; Odds ratio = 0.636, Pdominant = 0.012; Odds ratio = 0.664, Pover-dominant = 0.025; Odds ratio = 0.655, Pcodominant1 = 0.021) and rs499952 (Odds ratio = 0.807, Padditive = 0.032; Odds ratio = 0.643, Pcodominant2 = 0.034) polymorphisms were associated with a lower risk of subclinical atherosclerosis. On the other hand, the rs2155209 polymorphism was associated with a reduced risk of having a coronary artery calcification score ≥ 100 Agatston units. The rs13447720, rs499952, and rs2155209 polymorphisms, as well as the haplotypes that included the five studied polymorphisms were associated with some clinical and metabolic parameters in both subclinical atherosclerosis and healthy individuals. Our results suggest that the rs13447720 and rs499952 polymorphisms are associated with a decreased risk of developing subclinical atherosclerosis, whereas the rs2155209 is associated with a lower subclinical atherosclerosis severity (coronary artery calcification < 100 Agatston units). MRE11A polymorphisms and haplotypes were associated with clinical and metabolic parameters.

| S-EPMC6555271 | biostudies-literature

A haplotype of the phosphodiesterase 4D (PDE4D) gene is associated with myocardial infarction and with cardiometabolic parameters: the GEA study.

Project description:The phosphodiesterase family is involved in a wide spectrum of diseases, including ischemic stroke. However, few studies have analyzed the relationship between phosphodiesterase 4D (PDE4D) and myocardial infarction (MI). Therefore, the aim of this research was to evaluate the association of the PDE4D gene polymorphisms with MI, and with cardiometabolic parameters in the Mexican population. Six polymorphisms (rs2910829, rs1423246, rs966221, rs4502776, rs13172481, and rs6869495) were genotyped in 1023 MI patients and 1105 healthy controls. A similar distribution of the six polymorphisms was observed in both studied groups. However, after evaluating the linkage disequilibrium, we detected a risk haplotype for MI (AGAGAA; OR = 1.148; P = 0.025). In addition, the polymorphisms were associated with the presence of some clinical and metabolic parameters (central obesity, hypertriglyceridemia, Aspartate transaminase >p75, Lipoprotein (a) >30 mg/dL, TAT >p75, fatty liver, and vitamin D <30 ng/dL) in healthy controls. The results suggest that in the Mexican population, a PDE4D haplotype is associated with increased risk of developing MI, and that PDE4D polymorphisms are independently associated with the presence of cardiometabolic parameters.

| S-EPMC6343085 | biostudies-literature

Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study.

Project description:(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54-79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.

| S-EPMC8301759 | biostudies-literature

Common Variants in IL-20 Gene are Associated with Subclinical Atherosclerosis, Cardiovascular Risk Factors and IL-20 Levels in the Cohort of the Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Project description:Inflammation has been involved in the development of atherosclerosis, type 2 diabetes mellitus, insulin resistance, and obesity. Interleukin 20 is a pro-inflammatory cytokine encoded by a polymorphic gene located in chromosome 1. The aim of the study was to evaluate the association of two IL-20 polymorphisms (rs1400986 and rs1518108) with subclinical atherosclerosis (SA), cardiovascular risk factors and IL-20 levels in a cohort of Mexican individuals. The polymorphisms were determined in 274 individuals with SA and 672 controls. Under different models, rs1400986 (OR = 0.51, Pcodominant1 = 0.0001; OR = 0.36, Pcodominant2 = 0.014; OR = 0.49, Pdominant = 0.0001 and OR = 0.55, Padditive = 0.0001) and rs1518108 (OR = 0.62, Pcodominant2 = 0.048 and OR = 0.79, Padditive = 0.048) were associated with a lower risk of SA. These polymorphisms were associated with cardiovascular risk factors in individuals with SA and controls. Controls with the rs1400986 TT genotype presented high levels of IL-20 (p = 0.031). In individuals with the rs1400986 CC genotype, we observed a negative correlation between IL-20 levels and total abdominal tissue (TAT), visceral abdominal tissue (VAT) and subcutaneous abdominal tissue (SAT). Our results indicate that the IL-20 rs1400986 and rs1518108 polymorphisms were associated with decreased risk of developing SA and with some cardiovascular risk factors in individuals with SA and healthy controls. Negative correlation between BMI and VAT/SAT ratio in individuals with rs1400986 CC genotype and among IL-20 levels and TAT, VAT and SAT was observed.

| S-EPMC7022804 | biostudies-literature

Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Project description:Background and aimsSubclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds.MethodsThe associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66).ResultsIn EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN.ConclusionOur results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.

| S-EPMC4738145 | biostudies-literature

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions.

Project description:BackgroundGenome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated.MethodA large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed.ResultsDifferent from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10-9) and eight suggestively significant variants (P < 1 × 10-6) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption.ConclusionThe present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis.

| S-EPMC9764595 | biostudies-literature

RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS).

Project description:BackgroundSingle nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women's Interagency HIV Study (WIHS).MethodsCCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel's method and haplotype association analyses were conducted among the three races separately.ResultsSNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41×10(-5)), rs11856930 among Whites (p=5.62×10(-4)), and rs2572204 among Blacks (p=2.45×10(-3)). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics.DiscussionConsistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function.

| S-EPMC3965606 | biostudies-literature

Raet1e Polymorphisms Are Associated with Increased Risk of Developing Premature Coronary Artery Disease and with Some Cardiometabolic Parameters: The GEA Mexican Study.

Project description:In an animal model, new evidence has been reported supporting the role of raet1e as an atherosclerosis-associated gene. Our objective was to establish if raet1e polymorphisms are associated with the risk of developing premature coronary artery disease (CAD) or with the presence of cardiometabolic parameters. After an informatic analysis, five polymorphisms were chosen and determined in 1158 patients with premature CAD and 1104 controls using 5' exonuclease TaqMan genotyping assays. Standardized questionnaires were applied to all participants to obtain family medical history, demographic information, history of nutritional habits, physical activity, alcohol consumption, and pharmacological treatment. The functional effect of the rs7756850 polymorphism was analyzed by luciferase assays. Under different models, adjusted by age, gender, body mass index, current smoking, and type 2 diabetes mellitus, the rs6925151 (OR = 1.250, p heterozygote = 0.026; OR = 1.268, p codominant1 = 0.034), rs9371533 (OR = 1.255, p heterozygote = 0.024), rs7756850 (OR = 1.274, p heterozygote = 0.016; OR = 1.294, p codominant1 = 0.031), and rs9383921 (OR = 1.232, p heterozygote = 0.037) polymorphisms were associated with increased risk of premature CAD. When compared to the rs7756850 G allele, the C allele showed a decreased luciferase activity. In premature CAD patients, associations with low levels of adiponectin, with a high presence of hypertension, and with high levels of gamma-glutamyltransferase and total cholesterol were observed. In healthy controls, associations with a decrease in LDL pattern B, aspartate aminotransaminase, and hypo-?-lipoproteinemia were detected. An association of the raet1e polymorphisms with an increased risk of developing premature CAD and with cardiometabolic parameters has been shown for the first time. In addition, the functional effect of the rs7756850 polymorphism was defined.

| S-EPMC6312582 | biostudies-literature

Association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease: the multi-ethnic study of atherosclerosis.

Project description:OBJECTIVE:We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic). METHODS AND RESULTS:Using an expanded sample of 7936 Multi-Ethnic Study of Atherosclerosis participants, phenotyped for measures of subclinical atherosclerosis, incident myocardial infarction, and cardiovascular disease, and genotyped through the SNP Health Association Resource project, we have now examined the genetic association of these phenotypes with 126 genotyped and imputed SCARB1 SNPs. We also performed stratified analyses to examine whether SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study of Atherosclerosis cohort provides strong evidence for the association of rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In sex-stratified analysis, we observed statistically significant association of rs10846744 with incident cardiovascular disease events in males (P=0.01). Examining analytical results from the Myocardial Infarction Genetics Consortium for replication, we observed further support for the association of rs10846744 with myocardial infarction. CONCLUSIONS:The SCARB1 SNP, rs10846744, exerts a major effect on subclinical atherosclerosis and incident cardiovascular disease in humans.

| S-EPMC6637944 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data