The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease

Akadam-Teker, Başak; Kurnaz, Ozlem; Çoşkunpınar, Ender; Aday, Aynur Dağlar; Küçükhüseyin, Özlem; Çakmak, Hüseyin Altuğ; Teker, Erhan; Buğra, Zehra; Öztürk, Oğuz; Yilmaz-Aydogan, Hülya

doi:10.1016/j.gene.2013.07.056

Cited by 12 publications

(8 citation statements)

References 22 publications

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“…Cholesterol is either derived from the diet or from de novo synthesis occurring mainly in the liver through the mevalonate pathway. This pathway comprises several critical enzymes such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase ( hmgcr ), farnesyl diphosphate synthase ( fdps ) farnesyl-diphosphate farnesyltransferase ( fdft1 ), and 2,3-oxidosqualene-lanosterol cyclase ( lss ) and 7-dehydrocholesterol reductase ( dhcr7 )3536373839. All of these genes were significantly downregulated in 96hpf mahi-mahi larvae by slick oil exposure (Fig.…”

Section: Discussionmentioning

confidence: 99%

Novel transcriptome assembly and comparative toxicity pathway analysis in mahi-mahi (Coryphaena hippurus) embryos and larvae exposed to Deepwater Horizon oil

Mager

Grosell

et al. 2017

Sci Rep

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The impacts of Deepwater Horizon (DWH) oil on morphology and function during embryonic development have been documented for a number of fish species, including the economically and ecologically important pelagic species, mahi-mahi (Coryphaena hippurus). However, further investigations on molecular events and pathways responsible for developmental toxicity have been largely restricted due to the limited molecular data available for this species. We sought to establish the de novo transcriptomic database from the embryos and larvae of mahi-mahi exposed to water accommodated fractions (HEWAFs) of two DWH oil types (weathered and source oil), in an effort to advance our understanding of the molecular aspects involved during specific toxicity responses. By high throughput sequencing (HTS), we obtained the first de novo transcriptome of mahi-mahi, with 60,842 assembled transcripts and 30,518 BLAST hits. Among them, 2,345 genes were significantly regulated in 96hpf larvae after exposure to weathered oil. With comparative analysis to a reference-transcriptome-guided approach on gene ontology and tox-pathways, we confirmed the novel approach effective for exploring tox-pathways in non-model species, and also identified a list of co-expressed genes as potential biomarkers which will provide information for the construction of an Adverse Outcome Pathway which could be useful in Ecological Risk Assessments.

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Section: Discussionmentioning

confidence: 99%

Novel transcriptome assembly and comparative toxicity pathway analysis in mahi-mahi (Coryphaena hippurus) embryos and larvae exposed to Deepwater Horizon oil

Mager

Grosell

et al. 2017

Sci Rep

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“…A recent study showed that lipid-associated loci arestrongly associated with other components of the metabolic syndrome, including SBP and DBP with excess associations of 2.5-fold and 3.7-fold[5], respectively. We ignored the possible modulation of gene-age interactions by gender[16-17]and adjusted for the use of lipid-altering medications through a dichotomous (yes/no) covariate; this crude adjustment ignored both the dosage (which is not available in this study) and exact medication taken.…”

Section: Discussionmentioning

confidence: 99%

Linkage analysis incorporating gene–age interactions identifies seven novel lipid loci: The Family Blood Pressure Program

et al. 2014

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OBJECTIVE To detect novel loci with age-dependent effects on fasting (≥8 hours) levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides using3,600 African Americans, 1,283 Asians, 3,218 European Americans, and 2,026 Mexican Americans from the Family Blood Pressure Program (FBPP). METHODS Within each subgroup (defined by network, race, and sex), we employedstepwise linear regression (retention p≤0.05) to adjust lipid levels for age, age-squared, age-cubed,body-mass-index, current smoking status, current drinking status, field center, estrogen therapy (females only), as well asantidiabetic, antihypertensive, and antilipidemic medication use. For each trait, we pooled the standardized male and female residuals within each network and race and fit a generalized variance components model that incorporated gene-age interactions. We conducted FBPP-wide and race-specific meta-analyses by combining the p-values of each linkage marker across subgroups usinga modifiedFisher's method. RESULTS We identified seven novel loci with age-dependent effects; four total cholesterol loci from the meta-analysis of Mexican Americans (on chromosomes 2q24.1, 4q21.21, 8q22.2, and 12p11.23) and three high-density lipoprotein loci from the meta-analysis of all FBPP subgroups (on chromosomes 1p12, 14q11.2, and 21q21.1). These loci lacked significant genome-wide linkage or association evidence in the literature and hadlogarithm of odds (LOD) score ≥ 3 in the meta-analysis with LOD≥1 in at least two network and race subgroups (exclusively of non-European descent). CONCLUSION Incorporating gene-age interactions into the analysis of lipids using multi-ethnic cohorts can enhance gene discovery. These interaction loci can guide the selection of familiesfor sequencingstudies of lipid-associated variants.

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“…A promoter polymorphism (C911A; rs3761740) of the HMGCR gene was shown to be associated with TC level in Turkish males in a population-based case–control study [121], however the association was not observed in a candidate gene study of case–control design conducted in Western India [122]. Several GWAS and meta-analyses have identified multiple variants of HMGCR gene that are associated with TC and LDL-C levels [15, 16, 19, 20, 22–24, 26, 38, 94].…”

Section: Genetic Basis Of Polygenic Hypercholesterolemia – the Genes mentioning

confidence: 99%

Genetic determinants of inherited susceptibility to hypercholesterolemia – a comprehensive literature review

2017

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Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. This indicates the probability of having other genes with a causative or contributory role in the pathogenesis of hypercholesterolemia and suggests a polygenic inheritance of this condition. Here in, we review the recent evidence of association of the genetic variants with hypercholesterolemia and the three lipid traits; total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C), their biological pathways and the associated pathogenetic mechanisms. Nearly 80 genes involved in lipid metabolism (encoding structural components of lipoproteins, lipoprotein receptors and related proteins, enzymes, lipid transporters, lipid transfer proteins, and activators or inhibitors of protein function and gene transcription) with single nucleotide variants (SNVs) that are recognized to be associated with hypercholesterolemia and serum lipid traits in genome-wide association studies and candidate gene studies were identified. In addition, genome-wide association studies in different populations have identified SNVs associated with TC, HDL-C and LDL-C in nearly 120 genes within or in the vicinity of the genes that are not known to be involved in lipid metabolism. Over 90% of the SNVs in both these groups are located outside the coding regions of the genes. These findings indicates that there might be a considerable number of unrecognized processes and mechanisms of lipid homeostasis, which when disrupted, would lead to hypercholesterolemia. Knowledge of these molecular pathways will enable the discovery of novel treatment and preventive methods as well as identify the biochemical and molecular markers for the risk prediction and early detection of this common, yet potentially debilitating condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0488-4) contains supplementary material, which is available to authorized users.

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The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease

Cited by 12 publications

References 22 publications

Novel transcriptome assembly and comparative toxicity pathway analysis in mahi-mahi (Coryphaena hippurus) embryos and larvae exposed to Deepwater Horizon oil

Novel transcriptome assembly and comparative toxicity pathway analysis in mahi-mahi (Coryphaena hippurus) embryos and larvae exposed to Deepwater Horizon oil

Linkage analysis incorporating gene–age interactions identifies seven novel lipid loci: The Family Blood Pressure Program

Genetic determinants of inherited susceptibility to hypercholesterolemia – a comprehensive literature review

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