Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort

Mazzotti, Diego R.; Singulane, Cristiane Carvalho; Ota, Vanessa Kiyomi; Rodrigues, Thiago Potrich; Furuya, Tatiane Katsue; Souza, Fernando Henrique Carlos de; Cordeiro, Bruna Grassiela; Amaral, Camilla Magalhães de Oliveira; Chen, Elizabeth; Jacomini, Anielli; Smith, Marı́lia de Arruda Cardoso; Borsatto-Galera, Bianca

doi:10.1016/j.gene.2013.11.040

Cited by 15 publications

(10 citation statements)

References 47 publications

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“…In particular, expression of MMP9, a gene up-regulated only in the Obese B group, showed positive correlations with levels of plasma lipids (total cholesterol, non-HDL-cholesterol and LDL-cholesterol), apo B, glucose-regulating hormones (insulin, C-peptide and glucagon), insulin resistance marker (HOMA-IR) and leptin as well as BMI, suggesting a link between obesity and related metabolic disturbances such as dysregulation of lipid and glucose metabolism. Recently, Mazzotti et al (21) also reported an association of MMP9 polymorphisms with higher LDL-cholesterol levels. Among other TGF-β signalling-related genes down-regulated only in the Obese B group, loss of CD44 or CD47 induced adiposity or impaired glucose tolerance in mice fed a high-fat diet (22,23) .…”

Section: Comparison Of Inflammatory and Fibrotic Gene Expressions In mentioning

confidence: 97%

Differences in metabolic biomarkers in the blood and gene expression profiles of peripheral blood mononuclear cells among normal weight, mildly obese and moderately obese subjects

et al. 2016

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We compared metabolic biomarkers in the blood and peripheral blood mononuclear cell (PBMC) gene expression profiles among normal weight (BMI, 18·5-23 kg/m 2 ), mildly obese (BMI, 25-27·5 kg/m 2 ) and moderately obese Korean adult men (BMI, 27·5-30 kg/m 2 ). High leptin, lipids (except LDL-and HDL-cholesterol) and apoB levels and low adiponectin and HDL-cholesterol levels were present in the plasma of both mildly and moderately obese subjects. Circulating levels of inflammatory cytokines and markers of insulin resistance, oxidative stress and liver damage were altered in moderately obese subjects but not in mildly obese subjects. PBMC transcriptome data showed enrichment of pathways involved in energy metabolism, insulin resistance, bone metabolism, cancer, inflammation and fibrosis in both mildly and moderately obese subjects. Signalling pathways involved in oxidative phosphorylation, TAG synthesis, carbohydrate metabolism and insulin production; mammalian target of rapamycin, forkhead box O, ras-proximate-1, RAS and transforming growth factor-β signalling; as well as extracellular matrix-receptor interaction were enriched only in moderately obese subjects, indicating that changes in PBMC gene expression profiles, according to metabolic disturbances, were associated with the development and/or aggravation of obesity. In particular, fourteen and fifteen genes differentially expressed only in mildly obese subjects and in both mildly and moderately obese subjects, respectively, could be used as early or stable biomarkers for diagnosing and treating obesity-associated metabolic disturbance. We characterised BMI-associated metabolic and molecular biomarkers in the blood and provided clues about potential blood-based targets for preventing or treating obesityrelated complications.

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Section: Comparison Of Inflammatory and Fibrotic Gene Expressions In mentioning

confidence: 97%

Differences in metabolic biomarkers in the blood and gene expression profiles of peripheral blood mononuclear cells among normal weight, mildly obese and moderately obese subjects

et al. 2016

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“…More important, we showed that patients with TT genotype had significantly more robust LDL-C lowering effect in response to simvastatin treatment than those with CC genotype. Although the association of LDL-C level with MMP9 polymorphism has been reported in other studies [32, 33], this study is the first to demonstrate that MMP9 polymorphism is associated with LDL-C lowering efficacy after simvastatin treatment, and thus provides new evidences on the link of genetic variations to the efficacy of lipid lowering medications.…”

Section: Discussionmentioning

confidence: 57%

Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease

Wang

Zhi

et al. 2017

BMC Pharmacol Toxicol

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BackgroundGenetic variation of matrix metalloproteinase 9 (MMP-9) gene polymorphism has been suggested to modulate coronary heart diseases (CHD), yet the underlying mechanisms are not well understood.MethodsWe investigated the association of MMP9 rs3918242 single nucleotide polymorphism with inflammation and lipid-lowering efficacy after simvastatin treatment in Chinese patients with CHD. Fasting serum lipid profile and plasma inflammatory mediators were determined at baseline in 264 patients with CHD and 186 healthy control subjects, and after HMG-CoA reductase inhibitor simvastatin treatment (20 mg/day) for 12 weeks in CHD subjects.ResultsWe found that plasma MMP-9, TNF-α and IL-10 levels were significantly elevated in patients with CHD compared to control subjects before treatment. The plasma MMP9 in CHD patients carrying rs3918242 CC, CT and TT genotypes were comparable. Interestingly, CHD patients carrying TT genotype had significantly higher level of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) than those carrying CC genotype (P <0.05). Simvastatin treatment significantly reduced LDL-C, TG and plasma inflammatory mediator levels in CHD patients. The reduction of LDL-C upon simvastatin therapy was significantly greater in patients carrying TT genotype than those carrying CC genotype (P <0.05).ConclusionsMMP9 rs3918242 TT genotype is associated with elevated serum TG and LDL-C, and enhanced LDL-C-lowering response upon simvastatin treatment in Chinese patients with CHD.Clinical trial registrationThis study was retrospectively registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-ROC-17010971) on March 23rd 2017.

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“…ε4 allele carriers had the highest cholesterol and low-density lipoprotein values, followed by carriers of the ε3 allele, with ε2 allele carriers having the lowest values [24]. It has also been suggested that the presence of the ε2 allele reduces low-density lipoprotein [25] and that the ε4 allele increases low-density lipoprotein [26]. These findings are in agreement with our results in elderly patients with schizophrenia; serum cholesterol and low-density lipoprotein values were significantly lower in patients with the ε2 allele, while they were significantly higher in patients with the ε4 allele.…”

Section: Discussionmentioning

confidence: 99%

Low prevalence of lipid metabolism abnormalities in APOE ε2-genotype and male patients 60 years or older with schizophrenia

et al. 2017

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BackgroundSchizophrenia is a serious mental disorder largely manageable with atypical antipsychotics; however, these drugs have been associated with glucose/lipid metabolism issues such as diabetes and hyperlipidaemia. Apolipoprotein E (APOE) is the most abundant apolipoprotein, and APOE genotypes have been correlated with lipid metabolism phenotypes in an age-dependent manner. Studies examining the relationship between the APOE genotype and lipid abnormalities in patients with schizophrenia have been inconclusive, but primarily focused on adult patient populations. Therefore, we explored the correlations between the APOE genotype and glucose/lipid metabolism indicators and abnormalities in hospitalized patients 60 years or older with schizophrenia with a history of long-term antipsychotics use.MethodsWe assessed APOE genotype, age, weight, height, blood glucose, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein in a total of 294 patients. APOE genotypes were divided into three groups: APOE ε2 (ε2/ε2 and ε2/ε3), APOE ε3 (ε3/ε3), and APOE ε4 (ε3/ε4 and ε4/ε4), and comparisons were conducted among these groups or according to ε2 carrier status.Results APOE ε3/ε3 was the most common genotype (68.3%) and at least one ε3 allele was present in 81.8% of patients. There were no differences in antipsychotics type or dose according to the APOE genotype, but serum cholesterol values varied near significantly (P = 0.052) and low-density lipoprotein values varied significantly according to genotype (P < 0.05, lowest in the APOE ε2 genotype). Men had lower cholesterol and low-density lipoprotein levels (P < 0.05) than women. Compared to patients administered typical antipsychotics, those administered atypical antipsychotics had higher triglyceride, cholesterol, and low-density lipoprotein levels (P < 0.05). Stepwise linear regressions showed that cholesterol and low-density lipoprotein levels were influenced by sex, the APOE ε2 genotype, and atypical antipsychotics use.ConclusionsIn the context of atypical antipsychotics use, carriers of the APOE ε2-genotype and male patients with schizophrenia 60 years or older may be less likely to develop a lipid metabolism abnormality.

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Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort

Cited by 15 publications

References 47 publications

Differences in metabolic biomarkers in the blood and gene expression profiles of peripheral blood mononuclear cells among normal weight, mildly obese and moderately obese subjects

Differences in metabolic biomarkers in the blood and gene expression profiles of peripheral blood mononuclear cells among normal weight, mildly obese and moderately obese subjects

Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease

Low prevalence of lipid metabolism abnormalities in APOE ε2-genotype and male patients 60 years or older with schizophrenia

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