Susceptible gene polymorphism in patients with three-vessel coronary artery disease

Liu, Ru; Song, Lei; Jiang, Lin; Tang, Xiaofang; Xu, Lianjun; Gao, Zhan; Zhao, Xueyan; Xu, Jingjing; Gao, Runlin; Yuan, Jinqing

doi:10.1186/s12872-020-01449-6

Cited by 10 publications

(8 citation statements)

References 25 publications

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“…Apart from genetic mapping, GWAS and NGS studies have also explored the clinical utility of genetic biomarkers for the creation of genetic risk scores [ 10 , 11 , 36 , 41 ]. These algorithms would ideally predict the severity of CAD and the subsequent adverse outcomes aiming to identify patients with potential benefit from preventive care.…”

Section: Discussionmentioning

confidence: 99%

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The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study

Vizirianakis

Chatzopoulou

Papazoglou

et al. 2021

BMC Cardiovasc Disord

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Background Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide and is associated with multiple inherited and environmental risk factors. This study is designed to identify, design, and develop a panel of genetic markers that combined with clinical and angiographic information, will facilitate the creation of a personalized risk prediction algorithm (GEnetic Syntax Score—GESS). GESS score could be a reliable tool for predicting cardiovascular risk for future adverse events and for guiding therapeutic strategies. Methods GESS (ClinicalTrials.gov Identifier: NCT03150680) is a prospective, non-interventional clinical study designed to enroll 1080 consecutive patients with no prior history of coronary revascularization procedure, who undergo scheduled or emergency coronary angiography in AHEPA, University General Hospital of Thessaloniki. Next generation sequencing (NGS) technology will be used to genotype specific single-nucleotide polymorphisms (SNPs) across the genome of study participants, which were identified as clinically relevant to CAD after extensive bioinformatic analysis of literature-based SNPs. Enrichment analyses of Gene Ontology-Molecular Function, Reactome Pathways and Disease Ontology terms were also performed to identify the top 15 statistically significant terms and pathways. Furthermore, the SYNTAX score will be calculated for the assessment of CAD severity of all patients based on their angiographic findings. All patients will be followed-up for one-year, in order to record any major adverse cardiovascular events. Discussion A group of 228 SNPs was identified through bioinformatic and pharmacogenomic analysis to be involved in CAD through a wide range of pathways and was correlated with various laboratory and clinical parameters, along with the patients' response to clopidogrel and statin therapy. The annotation of these SNPs revealed 127 genes being affected by the presence of one or more SNPs. The first patient was enrolled in the study in February 2019 and enrollment is expected to be completed until June 2021. Hence, GESS is the first trial to date aspiring to develop a novel risk prediction algorithm, the GEnetic Syntax Score, able to identify patients at high risk for complex CAD based on their molecular signature profile and ultimately promote pharmacogenomics and precision medicine in routine clinical settings. Trial registration GESS trial registration: ClinicalTrials.gov Number: NCT03150680. Registered 12 May 2017- Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03150680.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, weighted multi-locus risk scores have been created to predict recurrent vascular events or statin efficacy and atherosclerotic burden alterations in CAD populations [ 10 , 47 – 49 ]. Nevertheless, limited data exist about the utility of genetic risk scores for the prediction of MACCE [ 11 – 13 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study

Vizirianakis

Chatzopoulou

Papazoglou

et al. 2021

BMC Cardiovasc Disord

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“…AA, amino acid; D, disintegrin-like; M, metalloproteinase; S, spacer. c.4221C.A was significantly more frequent in populations with major adverse cardiac events, cerebrovascular events, 91 and Thai malaria. 92 Overall, although the effect from single sSNVs is not dramatic, coexistence of 2 or more variants may have a synergistic effect and cause significant changes in ADAMTS13 functions.…”

Section: Discussionmentioning

confidence: 94%

Synonymous ADAMTS13 variants impact molecular characteristics and contribute to variability in active protein abundance

et al. 2022

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The effects of synonymous single nucleotide variants (sSNVs) are often neglected since they do not alter protein primary structure. Nevertheless, there is growing evidence that synonymous variations may impact mRNA expression, protein conformation and activity which may lead to protein deficiency and disease manifestations. As there are more than 21 million possible sSNVs affecting human genome, it is not feasible to experimentally validate the effect of each sSNV. Here, we report a comprehensive series of in-silico analyses assessing sSNV impact on a specific gene. A Disintegrin-like and Metalloprotease with Thrombospondin type-1 repeats, member-13 (ADAMTS13) was chosen as a model for its large size, many previously reported sSNVs and associated coagulopathy thrombotic thrombocytopenic purpura (TTP). Using various prediction tools of biomolecular characteristics, we evaluated all ADAMTS13 sSNVs registered in the NCBI dbSNP, including 357 neutral sSNVs and 19 sSNVs identified in TTP patients. We showed that some sSNVs change mRNA folding energy/stability, disrupt mRNA splicing, disturb micro RNAs (miRNAs) binding sites, and alter synonymous codon or codon pair usage. Our findings highlight the importance of considering sSNVs when assessing the complex effects of ADAMTS13 alleles and our approach provides a generalizable framework to characterize sSNV impact in other genes and diseases.

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“…Briefly, the ligation reaction was performed in an ABI2720 thermal cycler, and ABI3730XL sequencer was used to separate and detect PCR products by capillary electrophoresis. Raw data were further analyzed through the labeling dye color and fragment size of the allele-specific ligation-PCR product [ 15 ]. Then, 5% duplicate samples were tested to identify genotyping quality and were consistent with the original genotyping results.…”

Section: Methodsmentioning

confidence: 99%

NLRP3 Susceptible Gene Polymorphisms in Patients with Primary Gouty Arthritis and Hyperuricemia

Zhang

Kahaer

Zhang

et al. 2022

BioMed Research International

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Polymorphisms have been identified to predispose to primary gouty arthritis (GA) and hyperuricemia (HUA). Here, we accessed the five polymorphisms of rs10754558, rs35829419, rs3738448, rs3806268, and rs7525979 in NLRP3 on GA and HUA susceptibility. We collected 1198 samples (314 GA, 377 HUA, and 507 controls) for this case-control study. Our data detected that the rs3806268 (GA vs. AA: OR = 0.65 , p = 0.012 ) was significantly associated with the susceptibility to GA. The rs3738448 (TT vs. GG: OR = 2.05 , p = 0.024 ) and rs7525979 (TT vs. CC: OR = 1.96 , p = 0.037 ) were significantly associated with the susceptibility to HUA. The rs3806268 AG genotype presented decreased risk of GA among the hypertension ( OR = 0.54 , p = 0.0093 ), smoking ( OR = 0.59 , p = 0.018 ), and no obesity ( OR = 0.60 , p = 0.0097 ) subjects compared to the GG genotype group. The rs3738448 TT genotype demonstrated increased risk of HUA among the hypertension ( OR = 4.10 , p = 0.0056 ) and no drinking population ( OR = 3.56 , p = 0.016 ) compared to the GG genotype group. The rs7525979 TT genotype demonstrated increased risk of HUA among the hypertension ( OR = 4.01 , p = 0.0064 ) and no drinking population ( OR = 3.24 , p = 0.034 ) compared to the CC genotype group. Furthermore, a significant haplotype effect of rs10754558/C-rs35829419/C-rs3738448/G-rs3806268/A-rs7525979/C was found ( OR = 1.60 , p = 0.0046 ) compared with GCGAC haplotype. Bioinformatics analyses indicated that rs3738448, rs3806268, and rs7525979 might influence the gene regulation, while the T-allele of rs3738448 increased the stability of NLRP3-mRNA. Collectively, our case-control study confirms NLRP3 polymorphisms might participate in regulating immune and inflammation responses in GA and HUA.

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Susceptible gene polymorphism in patients with three-vessel coronary artery disease

Cited by 10 publications

References 25 publications

The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study

The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study

Synonymous ADAMTS13 variants impact molecular characteristics and contribute to variability in active protein abundance

NLRP3 Susceptible Gene Polymorphisms in Patients with Primary Gouty Arthritis and Hyperuricemia

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