Influence of APOA5 (rs662799 and rs3135506) gene polymorphism in acute myocardial infarction patients and its association with basic coronary artery disease risk factors

Srivastava, Rohit; Singh, Pratibha; Verma, Pratima; Sethi, Rishi; Verma, Arti; Ali, Wahid; Tiwari, Sunita

doi:10.7324/japs.2015.50602

Cited by 5 publications

(1 citation statement)

References 17 publications

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“…NGS analysis revealed the presence of a heterozygous missense variant c.56C > G (rs3135506) in APOA5 gene. This variant has previously been associated with an increased risk of hypertriglyceridemia [ 16 , 17 ], but current reports are more likely to indicate this as functional polymorphism [ 18 , 19 ]. As our patient did not demonstrate high TG concentration and the c.56C > G variant still did not explain the cause of hypercholesterolemia, further genetic diagnostics was required.…”

Section: Resultsmentioning

confidence: 99%

Identification of New Copy Number Variation and the Evaluation of a CNV Detection Tool for NGS Panel Data in Polish Familial Hypercholesterolemia Patients

Rutkowska

Pinkier

Sałacińska

et al. 2022

Genes

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Familial hypercholesterolemia (FH) is an inherited, autosomal dominant metabolic disorder mostly associated with disease-causing variant in LDLR, APOB or PCSK9. Although the dominant changes are small-scale missense, frameshift and splicing variants, approximately 10% of molecularly defined FH cases are due to copy number variations (CNVs). The first-line strategy is to identify possible pathogenic SNVs (single nucleotide variants) using multiple PCR, Sanger sequencing, or with more comprehensive approaches, such as NGS (next-generation sequencing), WES (whole-exome sequencing) or WGS (whole-genome sequencing). The gold standard for CNV detection in genetic diagnostics are MLPA (multiplex ligation-dependent amplification) or aCGH (array-based comparative genome hybridization). However, faster and simpler analyses are needed. Therefore, it has been proposed that NGS data can be searched to analyze CNV variants. The aim of the study was to identify novel CNV changes in FH patients without detected pathogenic SNVs using targeted sequencing and evaluation of CNV calling tool (DECoN) working on gene panel NGS data; the study also assesses its suitability as a screening step in genetic diagnostics. A group of 136 adult and child patients were recruited for the present study. The inclusion criteria comprised at least “possible FH” according to the Simon Broome diagnostic criteria in children and the DLCN (Dutch Lipid Clinical Network) criteria in adults. NGS analysis revealed potentially pathogenic SNVs in 57 patients. Thirty selected patients without a positive finding from NGS were subjected to MLPA analysis; ten of these revealed possibly pathogenic CNVs. Nine patients were found to harbor exons 4–8 duplication, two harbored exons 6–8 deletion and one demonstrated exon 9–10 deletion in LDLR. To test the DECoN program, the whole study group was referred for bioinformatic analysis. The DECoN program detected duplication of exons 4–8 in the LDLR gene in two patients, whose genetic analysis was stopped after the NGS step. The integration of the two methods proved to be particularly valuable in a five-year-old girl presenting with extreme hypercholesterolemia, with both a pathogenic missense variant (c.1747C>T) and exons 9–10 deletion in LDLR. This is the first report of a heterozygous deletion of exons 9 and 10 co-occurring with SNV. Our results suggest that the NGS-based approach has the potential to identify large-scale variation in the LDLR gene and could be further applied to extend CNV screening in other FH-related genes. Nevertheless, the outcomes from the bioinformatic approach still need to be confirmed by MLPA; hence, the latter remains the reference method for assessing CNV in FH patients.

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Section: Resultsmentioning

confidence: 99%

Identification of New Copy Number Variation and the Evaluation of a CNV Detection Tool for NGS Panel Data in Polish Familial Hypercholesterolemia Patients

Rutkowska

Pinkier

Sałacińska

et al. 2022

Genes

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Association of c.56C > G (rs3135506) Apolipoprotein A5 Gene Polymorphism with Coronary Artery Disease in Moroccan Subjects: A Case-Control Study and an Updated Meta-Analysis

Morjane

Charoute

Ouatou

et al. 2020

Cardiology Research and Practice

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Purpose. Coronary artery diseases (CAD) are clinical cardiovascular events associated with dyslipidemia in common. The interaction between environmental and genetic factors can be responsible for CAD. The present paper aimed to examine the association between c.56C > G (rs3135506) APOA5 gene polymorphism and CAD in Moroccan individuals and to perform an association update meta-analysis. Materials and Methods. The c.56C > G variant was genotyped in 122 patients with CAD and 134 unrelated controls. Genetic association analysis and comparison of biochemical parameters were performed using R statistical language. In addition, a comprehensive meta-analysis including eleven published studies in addition to our case-control study results was conducted using Review Manager 5.3. Publication bias was examined by Egger’s test and funnel plot. Results. The case-control study data showed that the c.56C > G polymorphism was associated with CAD susceptibility under codominant (P-value = 0.001), recessive (P-value <0.001) and log-additive (P-value = 0.008) inheritance models. In addition, this polymorphism was significantly associated with increased levels of systolic and diastolic blood pressures, triglycerides, glycemia, and total cholesterol. Furthermore, meta-analysis showed a significant association between the c.56C > G gene polymorphism and increased risk of CAD under recessive (OR = 3.39[1.77–6.50], P value <0.001) and homozygote codominant (OR = 3.96[2.44–6.45], P value <0.001) models. Conclusion. Our case-control study revealed a significant association between c.56C > G polymorphism and CAD in the Moroccan population. In addition, meta-analysis data supported the implication of this polymorphism in CAD susceptibility.

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Association between APOA5 polymorphisms and susceptibility to metabolic syndrome: a systematic review and meta-analysis

Mozafari,

Ashoori,

Emami Meybodi

et al. 2024

BMC Genomics

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Background The association between Apolipoprotein A5 (APOA5) genetic polymorphisms and susceptibility to metabolic syndrome (MetS) has been established by many studies, but there have been conflicting results from the literature. We performed a meta-analysis of observational studies to evaluate the association between APOA5 gene polymorphisms and the prevalence of MetS. Methods PubMed, Web of Science, Embase, and Scopus were searched up to April 2024. The random effects model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) of the association between APOA5 gene polymorphisms and the prevalence of MetS development. The potential sources of heterogeneity were evaluated by subgroup analyses and sensitivity analyses. Results A total of 30 studies with 54,986 subjects (25,341 MetS cases and 29,645 healthy controls) were included. The presence of rs662799 and rs651821 polymorphisms is associated with an approximately 1.5-fold higher likelihood of MetS prevalence (OR = 1.42, 95% CI: 1.32, 1.53, p < 0.001; I2 = 67.1%; P-heterogeneity < 0.001; and OR = 1.50, 95% CI: 1.36–1.65, p < 0.001), respectively. MetS is also more prevalent in individuals with the genetic variants rs3135506 and rs2075291. There was no evidence of a connection with rs126317. Conclusion The present findings suggest that polymorphisms located in the promoter and coding regions of the APOA5 gene are associated with an increased prevalence of MetS in the adult population. Identifying individuals with these genetic variations could lead to early disease detection and the implementation of preventive strategies to reduce the risk of MetS and its related health issues. However, because the sample size was small and there was evidence of significant heterogeneity for some APOA5 gene polymorphisms, these results need to be confirmed by more large-scale and well-designed studies.

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Influence of APOA5 (rs662799 and rs3135506) gene polymorphism in acute myocardial infarction patients and its association with basic coronary artery disease risk factors

Cited by 5 publications

References 17 publications

Identification of New Copy Number Variation and the Evaluation of a CNV Detection Tool for NGS Panel Data in Polish Familial Hypercholesterolemia Patients

Identification of New Copy Number Variation and the Evaluation of a CNV Detection Tool for NGS Panel Data in Polish Familial Hypercholesterolemia Patients

Association of c.56C > G (rs3135506) Apolipoprotein A5 Gene Polymorphism with Coronary Artery Disease in Moroccan Subjects: A Case-Control Study and an Updated Meta-Analysis

Association between APOA5 polymorphisms and susceptibility to metabolic syndrome: a systematic review and meta-analysis

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