Association Study of the ATP - Binding Cassette Transporter A1 (ABCA1) Rs2230806 Genetic Variation with Lipid Profile and Coronary Artery Disease Risk in an Iranian Population

Ghaznavi, Habib; Aali, Ehsan; Soltanpour, Mohammad Soleiman

doi:10.3889/oamjms.2018.063

Cited by 20 publications

(21 citation statements)

References 31 publications

(52 reference statements)

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“…A rs2230806 genetic variation was signi cantly related to the development and severity of coronary artery disease (CAD) in an Iranian population. Moreover, the K allele of ABCA1 R219K polymorphism has been shown to exert a protective effect against CAD risk and is correlated with decreased severity of CAD, independently of plasma lipid levels [69,70]. Here, we detected a g.18167532 T/C mutation of ABCA1.…”

Section: Relevance Of Gene Variants and Tail Fat Deposition Of Sheepmentioning

confidence: 59%

Comparative tail fat transcriptome analysis of key genes and pathways activated in response to fat deposition in two sheep breeds with extreme fat-tail phenotype differences

Zhang¹,

Xu²,

Wang³

et al. 2020

Preprint

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Background Fat tail in sheep presents a valuable energy reserve that has historically facilitated adaptation to harsh environments. However, in modern intensive and semi-intensive sheep industry systems, breeds with leaner tails are preferred. For efficient selection of lean sheep breeds, clarification of the regulatory mechanisms underlying tail fat deposition of sheep is crucial. Altay and Xinjiang Fine Wool (XFW) sheep, two important breeds with distinct tail fat deposition properties, are mainly distributed in the Xinjiang district of China, and serve as ideal models for investigating the mechanisms of tail fat deposition. In the present study, RNA-Seq was applied to determine the transcriptome profiles of tail fat tissues in these two breeds, followed by analysis of differentially expressed genes (DEGs) and their sequence variations. Results In total, 21,527 genes were detected, among which 3,965 displayed significant expression variations in tail fat tissues of the two sheep breeds, including 707 upregulated and 3,258 downregulated genes. Gene Ontology (GO) analysis disclosed that 198 DEGs were related to fat metabolism. In Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the majority were significantly enriched in adipocytokine signaling, PPAR signaling, and metabolic pathways, with some genes being involved in multiple pathways. Among the 198 DEGs, 22 genes were markedly up or down regulated in tail fat tissue of Altay sheep, supporting their association with the fat tail trait of this breed. A total of 41,724 and 42,193 SNPs were detected in tail fat tissue transcriptomes of Altay and XFW sheep, respectively. The distribution of 7 SNPs in the coding regions of the 22 candidate genes was further investigated in three sheep populations with distinct tail types. In particular, the g.18167532 T/C mutation of ABCA1 and g.57036072 G/T mutation of SLC27A2 showed significantly different distributions and were closely associated with tail type. Conclusions The present study provides transcriptomic evidence explaining the differences in fat- and thin-tailed sheep breeds and reveals numerous DEGs and SNPs associated with tail type. Our data provide a valuable theoretical basis for selection of lean sheep breeds.

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Section: Relevance Of Gene Variants and Tail Fat Deposition Of Sheepmentioning

confidence: 59%

Comparative tail fat transcriptome analysis of key genes and pathways activated in response to fat deposition in two sheep breeds with extreme fat-tail phenotype differences

Zhang¹,

Xu²,

Wang³

et al. 2020

Preprint

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“…Literature review of these 13 variants gives contradictory results about their functional significance. One study has found significant association of the variant rs2230806 in the ABCA1 gene with susceptibility to CHD [59], whereas other studies establish this variant to have a protective role against CHD risk [60,61]. There are no supportive literature data of the role of rs2271570 in the C4orf33 gene as a CHD risk factor.…”

Section: Prioritization Of Variants Called In the Young Healthy Indivmentioning

confidence: 99%

Prioritization of genetic variants predisposing to coronary heart disease in the Bulgarian population using centenarian exomes

Ganev

Balabanski

Serbezov

et al. 2019

Biotechnology & Biotechnological Equipment

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Coronary heart disease (CHD) is a major cause of mortality and morbidity in Europe. CHD is usually caused by atherosclerosis. Despite extensive studies that have identified a large number of genetic variants, strong evidence of association with CHD are not easily replicable in different populations. Two DNA pools were constructed: one with 32 Bulgarian centenarians and one with 61 young healthy Bulgarian individuals. The pools were whole-exome sequenced and variants were annotated and quality filtered (89,810 filtered variants). Allele frequencies were estimated and Fisher's exact test was used to evaluate the significance of allele frequency differences between the two pools. Two publicly available databases, Ensembl and DisGeNET, were used as a source of 2025 CHD-associated variants (CHD-AVs). These single nucleotide polymorphisms were screened in our data and 158 variants in 133 genes were found. ToppGene pathways analysis of genes called in both pools discovered participation of 37 genes in 9 significantly overrepresented pathways. Eight variants in these 37 genes have significantly higher frequency in young individuals, and are nominated for CHD association. Variants called only in the young individuals pool (13 variants) are also nominated for association with CHD. Based on sufficiently unambiguous literature data, from the nominated variants, we prioritize five as associated with CHD in the studied Bulgarian sample. Centenarian genomes can be used to provide additional information regarding the clinical relevance of genetic variants reported as associated with CHD.

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“…Until the present, about 97 mutations have been found in the ABCA1 gene, and a large number of them are linked with Tangier disease (TD), which is described as the accretion of cholesterol in reticuloendothelial cells that increases the risk of coronary heart disease [ 17 , 18 , 19 ]. In addition to Tangier disease [ 20 , 21 ], variations and alterations in the ABCA1 gene enhance the risk of allelic disorders, such as atherosclerosis [ 22 , 23 ], ischemic stroke [ 23 , 24 ], coronary heart disease [ 25 ], type II diabetes [ 26 , 27 , 28 ], myocardial infarction (MI) [ 6 ], familial hypercholesterolaemia (FH) [ 29 ], cancer [ 30 , 31 , 32 ], Alzheimer’s disease [ 33 ], and macular degeneration [ 34 ]. Mutations in the ABCA1 gene also increase the incidence of systemic and plaque inflammation [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Computational SNP Analysis and Molecular Simulation Revealed the Most Deleterious Missense Variants in the NBD1 Domain of Human ABCA1 Transporter

Dash

Ali

Rana

et al. 2020

IJMS

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The ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound exporter protein involved in regulating serum HDL level by exporting cholesterol and phospholipids to load up in lipid-poor ApoA-I and ApoE, which allows the formation of nascent HDL. Mutations in the ABCA1 gene, when presents in both alleles, disrupt the canonical function of ABCA1, which associates with many disorders related to lipid transport. Although many studies have reported the phenotypic effects of a large number of ABCA1 variants, the pathological effect of non-synonymous polymorphisms (nsSNPs) in ABCA1 remains elusive. Therefore, aiming at exploring the structural and functional consequences of nsSNPs in ABCA1, in this study, we employed an integrated computational approach consisting of nine well-known in silico tools to identify damaging SNPs and molecular dynamics (MD) simulation to get insights into the magnitudes of the damaging effects. In silico tools revealed four nsSNPs as being most deleterious, where the two SNPs (G1050V and S1067C) are identified as the highly conserved and functional disrupting mutations located in the NBD1 domain. MD simulation suggested that both SNPs, G1050V and S1067C, changed the overall structural flexibility and dynamics of NBD1, and induced substantial alteration in the structural organization of ATP binding site. Taken together, these findings direct future studies to get more insights into the role of these variants in the loss of the ABCA1 function.

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Association Study of the ATP - Binding Cassette Transporter A1 (ABCA1) Rs2230806 Genetic Variation with Lipid Profile and Coronary Artery Disease Risk in an Iranian Population

Cited by 20 publications

References 31 publications

Comparative tail fat transcriptome analysis of key genes and pathways activated in response to fat deposition in two sheep breeds with extreme fat-tail phenotype differences

Comparative tail fat transcriptome analysis of key genes and pathways activated in response to fat deposition in two sheep breeds with extreme fat-tail phenotype differences

Prioritization of genetic variants predisposing to coronary heart disease in the Bulgarian population using centenarian exomes

Computational SNP Analysis and Molecular Simulation Revealed the Most Deleterious Missense Variants in the NBD1 Domain of Human ABCA1 Transporter

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