Relationship of SELE A561C and G98T Variants With the Susceptibility to CAD

Liao, Bihong; Chen, Keqi; Wang, Xiong; Chen, Ruimian; Mai, Aihuan; Xu, Zefeng; Dong, Shaohong

doi:10.1097/md.0000000000001255

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…SELE encodes E-selectin; variants in SELE have been associated with coronary artery disease and hypertension 64–66 . BAG3 encodes for the Bcl2-associated athanogene 3 (BAG3) protein, a member of the BAG family of co-chaperones that interact with the heat shock protein 70 ATPase domain.…”

Section: Discussionmentioning

confidence: 99%

Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1

Gray

Kovacheva²,

Mirzakhani

et al. 2018

Hypertension

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The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant maternal and fetal morbidity, has been poorly characterized. To identify maternal genes associated with preeclampsia risk, we assembled 498 cases and 1864 controls of European ancestry from preeclampsia case-control collections in 5 different US sites (with additional matched population controls), genotyped samples on a cardiovascular gene-centric array composed of variants from ≈2000 genes selected based on prior genetic studies of cardiovascular and metabolic diseases and performed case-control genetic association analysis on 27 429 variants passing quality control. In silico replication testing of 9 lead signals with <10 was performed in independent European samples from the SOPHIA (Study of Pregnancy Hypertension in Iowa) and Inova cohorts (212 cases, 456 controls). Multiethnic assessment of lead signals was then performed in samples of black (26 cases, 136 controls), Hispanic (132 cases, 468 controls), and East Asian (9 cases, 80 controls) ancestry. Multiethnic meta-analysis (877 cases, 3004 controls) revealed a study-wide statistically significant association of the rs9478812 variant in the pleiotropic gene (odds ratio, 1.40 [1.23-1.60];=5.90×10). The rs9478812 effect was even stronger in the subset of European cases with known early-onset preeclampsia (236 cases diagnosed <37 weeks, 1864 controls; odds ratio, 1.59 [1.27-1.98]; =4.01×10). variants have previously been implicated in genome-wide association studies of blood pressure, body weight, and neurological disorders. Although larger studies are required to further define maternal preeclampsia heritability, this study identifies a novel maternal risk locus for further investigation.

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Section: Discussionmentioning

confidence: 99%

Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1

Gray

Kovacheva²,

Mirzakhani

et al. 2018

Hypertension

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“…Therefore, our results suggested that the associations between two SNPs (AGTR1/rs2638360 and VSNL1/rs16983422) and SSBP were consistent among different salt loading manners. The SELE gene is expressed in cytokine-stimulated endothelial cells and appears to participate in the pathogenesis of atherosclerosis ( Liao et al, 2016 ). In the GenSalt study, SELE/rs5368 was significantly associated with decreased BP responses to low-sodium processes only in male.…”

Section: Discussionmentioning

confidence: 99%

Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators

Xie

Liu

et al. 2021

Front. Genet.

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Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in candidate genes and SSBP and to estimate their interaction with potential risk factors. A total of 29 candidate SNPs were genotyped in the 2,057 northern Han Chinese population from the Systems Epidemiology Study on Salt Sensitivity. A modified Sullivan’s acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was used to identify SSBP. A generalized linear model was conducted to analyze the association between SNPs and SSBP, and Bonferroni correction was used for multiple testing. Mediation analysis was utilized to explore the mediation effect of risk factors. Eleven SNPs in eight genes (PRKG1, CYBA, BCAT1, SLC8A1, AGTR1, SELE, CYP4A11, and VSNL1) were identified to be significantly associated with one or more SSBP phenotypes (P < 0.05). Four SNPs (PRKG1/rs1904694 and rs7897633, CYP4A11/rs1126742, and CYBA/rs4673) were still significantly associated after Bonferroni correction (P < 0.0007) adjusted for age, sex, fasting blood glucose, total cholesterol, salt-eating habit, physical activity, and hypertension. Stratified analysis showed that CYBA/rs4673 was significantly associated with SSBP in hypertensive subjects (P < 0.0015) and CYP4A11/rs1126742 was significantly associated with SSBP in normotensive subjects (P < 0.0015). Subjects carrying both CYBA/rs4673-AA and AGTR1/rs2638360-GG alleles have a higher genetic predisposition to salt sensitivity due to the potential gene co-expression interaction. Expression quantitative trait loci analysis (eQTL) suggested that the above positive four SNPs showed cis-eQTL effects on the gene expression levels. Mediation analysis suggested that several risk factors were mediators of the relation between SNP and SSBP. This study suggests that the genetic variants in eight genes might contribute to the susceptibility to SSBP, and other risk factors may be the mediators.

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“…So far, mainly two presumably functional SELE polymorphisms, A561C (rs5361) and G98T (rs1805193), have been investigated in different ethnic groups with respect to CAD [13, 14, 26]. However, the haplotype-based analysis may offer greater power in association studies than the analysis of one SNP at a time, especially when none of the investigated SNPs is a causative marker [27].…”

Section: Discussionmentioning

confidence: 99%

E-selectin gene haplotypes are associated with the risk of myocardial infarction

Gorący

Kaczmarczyk

Ciechanowicz

et al. 2019

aoms

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IntroductionEndothelial dysfunction is one of the most important factors implicated in the pathogenesis of coronary artery disease (CAD). The aim of this study was to investigate the association of the E-selectin gene (SELE) with CAD and CAD-related traits using tagging polymorphisms.Material and methodsA total of 379 Polish patients who had undergone angiography were included: 261 patients with angiographically documented CAD, 202 CAD patients without myocardial infarction (CAD/MI(–) group) and 59 patients with myocardial infarction (CAD/MI(+) group) as well as 118 healthy control subjects (non-CAD). Eight tagging single nucleotide polymorphisms (SNPs) in the SELE gene were selected using genotype data from HapMap. Genotyping was performed using PCR-RFLP and PCR-DHPLC methods.ResultsThe most common SELE haplotype in this analysis ([C;G;T;C;G;T], 31.2%) showed a negative association with myocardial infarction (MI) (CAD/MI(+) vs. non-CAD) under the additive (p = 0.001), dominant (p = 0.006) and recessive (p = 0.012) model. Two other haplotypes ([C;G;C;C;A;C], [C;A;C;A;G;T], 5.73% and 18.1%, respectively) were also negatively associated with MI under the additive and dominant model. We also found two haplotypes ([T;G;T;C;G;T], [C;G;C;C;A;T], 1.52% and 6.71%, respectively) associated with the risk for MI (CAD/MI(+) vs. CAD/MI(–)), acting in both additive (p = 0.04, p = 0.007, respectively) and dominant (p = 0.04, p = 0.004, respectively) manner. There was no association with either CAD/MI(–) or with severity of CAD expressed as the number of vessels involved.ConclusionsOur results suggest that SELE is one of the independent genetic factors modifying the risk of myocardial infarction.

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Relationship of SELE A561C and G98T Variants With the Susceptibility to CAD

Cited by 11 publications

References 35 publications

Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1

Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1

Candidate Gene Polymorphisms Influence the Susceptibility to Salt Sensitivity of Blood Pressure in a Han Chinese Population: Risk Factors as Mediators

E-selectin gene haplotypes are associated with the risk of myocardial infarction

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