Las apolipoproteínas como marcadores predictivos de riesgo metabólico-vascular en pediatría / Apolipoproteins as predictive markers of metabolic-vascular risk in pediatrics

Introducción: La búsqueda de nuevos marcadores predictivos, en la estratificación de riesgos metabólicos-vasculares, es de vital importancia en la prevención, diagnóstico y tratamiento oportuno de enfermedades cardiometabólicas, al considerar que el proceso aterosclerótico se inicia desde la infancia. La revisión documental se realizó entre marzo y julio del 2022, consultadas las bases de datos PubMed/Medline, SciElo, Scopus y el Google académico como puerta de entrada de la información sobre el tema. Se revisaron 33 artículos originales en el período 2012-2021 en idioma inglés y español, referenciados 29 y los términos clave para la búsqueda fueron, riesgo metabólico-vascular, apolipoproteínas A1 y B100, marcadores predictores de riesgo metabólico-vascular, niñez, adolescencia. Objetivo: Analizar la importancia de las apolipoproteínas como marcadores predictores del riesgo metabólico- vascular pediátrico. Desarrollo: Las apolipoproteínas han surgido como una alternativa muy viable, particularmente la determinación de ApoB 100 y ApoA 1, que expresan el equilibrio entre la actividad aterogénica y la antiaterogénica y están presentes desde las edades tempranas de la vida. El diagnóstico temprano de estos marcadores, permitirá aplicar intervenciones precoces para propiciar cambios a estilos de vidas saludables, así como tratamientos preventivos que impidan las complicaciones de la enfermedad cardiometabólica. Conclusiones: Al considerar que el proceso aterosclerótico se inicia en edades tempranas, las apolipoproteínas constituyen marcadores en la predicción del riesgo metabólico-vascular, su determinación permite la identificación, estratificación del riesgo y propuesta de estrategias preventivas desde las edades pediátricas(AU)

Introduction: The search for new predictive markers, in the stratification of metabolic-vascular risks, is of vital importance in the prevention, diagnosis and timely treatment of cardiometabolic diseases, considering that the atherosclerotic process begins in childhood. The documentary review was carried out between March and July 2022, consulting the PubMed/Medline, SciElo, Scopus and Google Scholar databases as a gateway to information on the topic. 33 original articles were reviewed in the period 2012-2021 in English and Spanish, 29 were referenced and the key terms for the search were, metabolic-vascular risk, apolipoproteins A1 and B100, markers predictive of metabolic-vascular risk, childhood adolescence. Objective: To analyze the importance of apolipoproteins as predictive markers of pediatric metabolic-vascular risk. Development: Apolipoproteins have emerged as a very viable alternative, particularly the determination of ApoB 100 and ApoA 1, which express the balance between atherogenic and antiatherogenic activity and are present from the early ages of life. Early diagnosis of these markers will allow for early interventions to promote changes to healthy lifestyles, as well as preventive treatments that prevent complications of cardiometabolic disease. Conclusions: Considering that the atherosclerotic process begins at an early age, apolipoproteins constitute markers in the prediction of metabolic-vascular risk, their determination allows the identification, risk stratification and proposal of preventive strategies from pediatric ages(AU)

Apolipoprotein E enhances migration of endometrial cancer cells byactivating the ERK/MMP9 signaling pathway / 南方医科大学学报

OBJECTIVE@#To study the role of apolipoprotein E (APOE) in regulating endometrial cancer metastasis and explore the signaling pathway in the regulatory mechanism.@*METHODS@#Human endometrial cancer cell line HEC-1B was transfected with a control siRNA (siCtrl) or a specific siRNA targeting APOE (siAPOE) or with either pEGFP-N1 plasmid or an APOEoverexpressing plasmid. The changes in migration, proliferation, apoptosis and cell cycle of the transfected cells were examined using wound healing assay, Transwell migration assay, MTT assay, flow cytometry, and Hoechst staining. The activity of the ERK/MMP9 signaling pathway in the transfected cells was assessed using RT-qPCR and Western blotting. The expression level of APOE in clinical specimens of endometrial cancer tissues were detected using immunohistochemistry and its correlation with differentiation of endometrial cancer tissues was analyzed.@*RESULTS@#Wound healing assay and Transwell migration assay showed that compared with those in siCtrl group, HEC-1B cells transfected with siAPOE showed significantly reduced migration ability (P < 0.05), whereas APOE overexpression significantly promoted the migration of the cells (P < 0.05). Neither APOE knockdown nor overexpression produced significant effects on HEC-1B cell proliferation as shown by MTT assay and flow cytometry. Hoechst staining revealed that transfection with siAPOE did not significantly affect apoptosis of HEC-1B cells. APOE knockdown obviously reduced and APOE overexpression enhanced ERK phosphorylation and MMP9 expression in HEC-1B cells (P < 0.05). Treatment with U0126 partially reversed the effects of APOE overexpression on ERK phosphorylation, migration and MMP9 expression in HEC-1B cells (P < 0.05). APOE is highly expressed in clinical samples of endometrial cancer tissues as compared with the adjacent tissues.@*CONCLUSION@#APOE is highly expressed in endometrial cancer tissues to promote cancer cell migration by enhancing ERK phosphorylation and MMP9 expression.

Efficacy of apolipoprotein 2-Jifusheng in the treatment of osteomyelitis in rabbits / 中国骨伤

OBJECTIVE@#To evaluate the effect of one-stage treatment of bone morphogenetic protein 2 combined with Jifusheng in the experimental model of osteomyelitis in rabbits.@*METHODS@#The model of chronic osteomyelitis of tibia was established in 30 3-month-old male New Zealand white rabbits with a body weight of (2.0±0.5) kg, and the model was verified 4 weeks after operation. Thirty rabbits with osteomyelitis were randomly divided into 3 groups with 10 rabbits in each group (@*RESULTS@#At 4 weeks after operation, 30 rabbits with osteomyelitis were successfully validated. The results of serological examination showed that the hypersensitive C-reactive protein (CRP) and white blood cell count(WBC)in the model group were significantly higher than those in the blank group at 2 and 4 weeks after operation. Eight weeks after treatment, the detection of blood indexes showed that the white blood cell count (WBC)and hypersensitive C reactive protein (CRP)in treatment group A and treatment group B were significantly lower than those in the model group (@*CONCLUSION@#The combined application of apolipoprotein 2-Jifusheng can promote bone repair and reduce the inflammation of the focus. it can treat rabbits with osteomyelitis in one stage, provide objective basis for the formulation of clinical treatment strategy of osteomyelitis and further promote clinical research.

Quercetina Melhora o Perfil Lipídico e Apolipoproteico em Ratos Tratados com Glicocorticóides em Altas Doses / Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats

Resumo Fundamento Os glicocorticóides (GCs) são amplamente prescritos para o tratamento de numerosos distúrbios clínicos devido às suas propriedades anti-inflamatórias e imunomoduladoras, e um dos efeitos indesejáveis mais comuns desses medicamentos é a dislipidemia. Objetivo Avaliar o efeito da quercetina, um flavonoide derivado de plantas, no perfil lipídico de ratos tratados com glicocorticóides em altas doses. Métodos Um total de 32 ratos Sprague-Dawley foram distribuídos aleatoriamente entre quatro grupos (8 ratos por grupo) e tratados por 6 semanas com uma das seguintes opções : (i) solução salina normal; (ii) 40 mg/kg de succinato sódico de metilprednisolona (MP); (iii) MP + 50 mg/kg de quercetina; (iv) MP + 150 mg/kg de quercetina. O MP foi injetado por via subcutânea e a quercetina foi administrada por gavagem oral 3 dias por semana. No final do estudo, o perfil lipídico dos animais foi medido através de kits enzimáticos. Os dados foram analisados e a significância estatística foi estabelecida em p <0,05. Resultados Os níveis séricos médios de colesterol total (CT), triglicerídeos (TG) e LDL aumentaram drasticamente em animais tratados com GC em comparação com o grupo controle. Ambas as doses de quercetina (50 e 150 mg/kg) melhoraram o CT (43% e 45%), LDL (56% e 56%) e TG (46% e 55%, respectivamente). A razão Apo B/A1 diminuiu mais de 20% após a ingestão de Anti-Inflamatory Agents. Conclusões Esses dados sugerem que a ingestão de quercetina Quercetin; induzida por glicocorticóides. (Arq Bras Cardiol. 2020; 115(1):102-108)

Abstract Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.)

Trigliceridos/colesterol HDL: utilidad en la deteccion de sujetos obesos con riesgo para diabetes mellitus tipo 2 y enfermedad cardiovascular / Triglycerides/HDL cholesterol: utility for the detection of obese subjects with risk for diabetes mellitus type 2 and cardiovascular diseases / Triglicerideos/colesterol HDL: utilidade na deteccao de sujeitos obesos com risco para a diabetes mellitus tipo 2 e doenca cardiovascular

En la Republica Argentina, la prevalencia de obesidad se ha incrementado considerablemente y la de diabetes mellitus tipo 2 (DMT2) alcanza 12,7%. La obesidad presenta heterogeneidad y el aumento de la grasa abdominal puede incluir hipertrigliceridemia, hiperglucemia, disminucion de C-HDL, aumentos de apolipoproteina B (Apo B), aumento de lipoproteinas LDL pequenas y densas, hiperinsulinemia, insulino-resistencia (IR), estado inflamatorio cronico, estado protrombotico y otras alteraciones metabolicas, que se han reunido en el llamado sindrome metabolico con prevalencia del 20 al 40%. La resistencia a la insulina (IR) esta presente en 10 al 25% de la poblacion y se asocia con esas alteraciones. La determinacion de IR es compleja, necesita de internacion en clinicas y debe ser realizada por especialistas. En el laboratorio se puede estimar a traves del dosaje de insulina, pero no esta estandarizado, por lo que es necesario disponer de tecnicas sencillas y accesibles. La relacion trigliceridos (TG)/colesterol HDL (C-HDL) puede ser una opcion utilizando como valores de corte TG/C-HDL ≥2,5 en mujeres y ≥3,5 en varones. Se asocia significativamente con IR y enfermedad cardiovascular (ECV), tiene buena especificidad aunque bajo poder discriminador por lo cual cuando esta presente y existe riesgo de DMT2 o ECV deberia complementarse con el calculo del colesterol-no-HDL o Apo B y el colesterol remanente. Teniendo en cuenta la pandemia de obesidad y DMT2 y la elevada frecuencia de ECV, la relacion TG/C-HDL podria ser un marcador que deberia ser informado por el laboratorio bioquimico-clinico.

In Argentina, the prevalence of obesity has increased considerably and type 2 diabetes mellitus (DMT2) reaches 12.7%. Obesity presents heterogeneity and the increase in abdominal fat may include hypertriglyceridemia, hyperglycemia, decrease in HDL-C, increases in apolipoprotein B (Apo B), increase in small and dense LDL lipoproteins, hyperinsulinemia, insulin resistance (IR), chronic inflammatory state, prothrombotic state and other metabolic alterations, which have been included in the so-called metabolic syndrome with 20 to 40% prevalence. Insulin resistance is present in 10 to 25% of the population and is associated with these alterations. The determination of IR is complex; it needs hospitalization and must be performed by specialists. In the laboratory, it can be estimated through insulin dosing, but it is not standardized, so it is necessary to have simple and accessible techniques. The triglycerides (TG)/HDL cholesterol (HDL-C) ratio can be an option using TG/C-HDL cutoff values ≥2.5 in women and ≥3.5 in men. It is significantly associated with IR and CVD and has good specificity but low discriminating power. So when it is present and there is a risk of T2DM or cardiovascular disease, CVD should be complemented with the calculation of non-HDL cholesterol or Apo B and the remaining cholesterol. Considering the pandemic of obesity and DMT2 and the high frequency of CVD, the TG/C-HDL ratio marker should be reported by the biochemical-clinical laboratory.

Na Republica Argentina, a prevalencia de obesidade aumentou em forma consideravel e a de diabetes mellitus tipo 2 (DMT2) atinge 12,7%. A obesidade apresenta heterogeneidade e o aumento da gordura abdominal pode incluir hipertrigliceridemia, hiperglicemia, diminuicao do HDL-C, aumentos da apolipoproteina B (Apo B), aumento das lipoproteinas LDL pequenas e densas, hiperinsulinemia, resistencia a insulina, estado inflamatorio cronico, estado pro-trombotico e outras alteracoes metabolicas, que se encontraram na chamada sindrome metabolica, com prevalencia de 20 a 40%. A resistencia a insulina (RI) esta presente em 10 a 25% da populacao e esta associada a essas alteracoes. A determinacao da RI e complexa, precisa da hospitalizacao em clinicas e deve ser realizada por especialistas. No laboratorio, isso pode ser estimado atraves da dosagem de insulina, mas nao e padronizado, portanto e necessario ter tecnicas simples e acessiveis. A relacao triglicerideos (TG)/colesterol HDL (C-HDL) pode ser uma opcao usando como valores de corte TG/C-HDL ≥2,5 em mulheres e ≥3,5 em homens. Esta significativamente associado a RI e a doenca cardiovascular (DCV), possui boa especificidade, embora apresente baixo poder discriminador; portanto, quando esta presente e ha risco de DMT2 ou DCV, deveria ser complementado com o calculo do colesterol nao-HDL ou Apo B e o restante colesterol. Considerando a pandemia de obesidade e DMT2 e a alta frequencia de DCV, a relacao TG/C-HDL poderia ser um marcador que deveria ser relatado pelo laboratorio bioquimico-clinico.

Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial

BACKGROUND/OBJECTIVES: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. SUBJECTS/METHODS: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6 week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. RESULTS: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. CONCLUSION: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS. This trial is registered at ClinicalTrials.gov as NCT03267901.

A Critical Role of PCSK9 in Mediating IL-17-Producing T Cell Responses in Hyperlipidemia

We previously demonstrated that atherogenic Ldlr(−/−)Apobec1(−/−) (LDb) double knockout mice lacking both low-density lipoprotein receptor (LDLR) and apolipoprotein B mRNA-editing catalytic polypeptide-1 (Apobec1) had increased serum IL-17 levels, with T cell programming shifted towards Th17 cells. In this study, we assessed the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in T cell programming and atherogenesis. We deleted the Pcsk9 gene from LDb mice to generate Ldlr(−/−)Apobec1(−/−)Pcsk9(−/−) (LTp) triple knockout mice. Atherosclerosis in the aortic sinus and aorta were quantitated. Lymphoid cells were analyzed by flow cytometry, ELISA and real-time PCR. Despite of dyslipidemia, LTp mice developed barely detectable atherosclerotic lesions. The IL-17, was very low in plasma and barely detectable in the aortic sinus in the LTp mice. In the spleen, the number of CD4⁺CD8⁻ cells and splenocytes were much lower in the LDb mice than LTp mice, whereas, the IL-17-producing cells of γδTCR⁺ T cells and effector memory CD4⁺ T cells (CD44(hi)CD4⁺) in the spleen were significantly higher in the LDb mice than in the LTp mice. The Rorc mRNA expression levels were elevated in LDb mice compared to LTp mice. When re-stimulated with an anti-CD3 Ab, CD44(hi)CD4⁺ T cells from LDb mice secreted more IL-17 than those from LTp mice. T cells from LDb mice (with PCSK9) produce more IL-17 at basal and stimulated conditions when compared with LTp mice (without PCSK9). Despite the dyslipidemic profile and the lack of LDLR, atherogenesis is markedly reduced in LTp mice. These results suggest that PCSK9 is associated with changes in T cell programming that contributes to the development of atherosclerosis.

Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with 50 µM curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%–8.05% to 27.63%–35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by 50 µM curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the editosome in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Anhedonia and Dysphoria Are Differentially Associated with the Risk of Dementia in the Cognitively Normal Elderly Individuals: A Prospective Cohort Study

OBJECTIVE: We investigated the impact of depressed mood (dysphoria) and loss of interest or pleasure (anhedonia)on the risk of dementia in cognitively-normal elderly individuals. METHODS: This study included 2,685 cognitively-normal elderly individuals who completed the baseline and 4-year follow-up assessments of the Korean Longitudinal Study on Cognitive Aging and Dementia. We ascertained the presence of dysphoria and anhedonia using the Mini International Neuropsychiatric Inventory. We defined subjective cognitive decline as the presence of subjective cognitive complaints without objective cognitive impairments. We analyzed the association of dysphoria and anhedonia with the risk of cognitive disorders using multinomial logistic regression analysis adjusted for age, sex, education, Cumulative Illness Rating Scale score, Apolipoprotein E genotype, and neuropsychological test performance. RESULTS: During the 4-year follow-up period, anhedonia was associated with an approximately twofold higher risk of mild cognitive impairment (OR=2.09, 95% CI=1.20–3.64, p=0.008) and fivefold higher risk of dementia (OR=5.07, 95% CI=1.44–17.92, p=0.012) but was not associated with the risk of subjective cognitive decline. In contrast, dysphoria was associated with an approximately twofold higher risk of subjective cognitive decline (OR=2.06, 95% CI=1.33–3.19, p=0.001) and 1.7-fold higher risk of mild cognitive impairment (OR=1.75, 95% CI=1.00–3.05, p=0.048) but was not associated with the risk of dementia. CONCLUSION: Anhedonia, but not dysphoria, is a risk factor of dementia in cognitively-normal elderly individuals.

The Association between the Apolipoprotein E Gene Polymorphism and All-cause Mortality in the Korean Population

BACKGROUND: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. METHODS: This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. RESULTS: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97–1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74–0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97–1.20) and 0.80 (95% CI, 0.70–0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52–0.92) for the E2 allele and 1.25 (95% CI, 1.03–1.53) for the E4 allele. CONCLUSION: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.

The Potential Role of Biomarkers Associated with ASCVD Risk: Risk-Enhancing Biomarkers

Serum cholesterol is major risk factor and contributor to atherosclerotic cardiovascular disease (ASCVD). Therapeutic cholesterol-lowering drugs, especially statin, revealed that reduction in low-density lipoprotein cholesterol (LDL-C) produces marked reduction of ASCVD events. In the preventive scope, lower LDL-C is generally accepted as better in proven ASCVD patients and high-risk patient groups. However, in patients with low to intermediate risk without ASCVD, risk assessment is clinically guided by traditional major risk factors. In this group, the complement approach to detailed risk assessment about traditional major risk factors is needed. These non-traditional risk factors include ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, lipoprotein(a) (Lp[a]), apolipoprotein B (apoB), or coronary artery calcium (CAC) score. CAC measurements have an additive role in the decision to use statin therapy in non-diabetic patients 40–75 years old with intermediate risk in primary prevention. This review comprises ASCVD lipid/biomarkers other than CAC. The 2013 and 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines suggest these factors as risk-enhancing factors to help health care providers better determine individualized risk and treatment options especially regarding abnormal biomarkers. The recent 2018 Korean guidelines for management of dyslipidemia did not include these biomarkers in clinical decision making. The current review describes the current roles of hsCRP, ABI, LP(a), and apoB in personal modulation and management of health based on the 2018 ACC/AHA guideline on the management of blood cholesterol.

Apolipoprotein E Genotype and Expression Correlated with Hepatitis C Virus Genotype and Infection

The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. Several studies reported that HCV particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. However, the relationship between apoE gene polymorphisms and HCV genotypes in patients with HCV is less well understood. The aim of this study was to investigate the association between apoE gene polymorphism and HCV genotypes in patients. The HCV genotypes were identified among the 124 patients infected with HCV, and the genetic characteristics of the HCV genotype were analyzed. In addition, the results of the clinical laboratory test were comparatively analyzed according to the classified genotypes. Both HCV 1b (n=80) and 2a (n=42) patients had higher AFP, AST, ALT, ALP, γ-GTP, apoB, and apoE values compared with the normal control group. In particular, apoB and apoE levels were statistically significantly higher in the HCV 2a patients (P<0.05) and apoE levels were significantly higher in the HCV 1b patients (P<0.000). According to the results the patients with HCV genotype 1b showed higher values of liver damage related indicators and apoB expression than the patients with HCV genotype 2a. The fat related indicators and apoE expression were not different between the two major HCV genotypes (2a and 1b). We anticipate that the apoE ε3 allele is the most common type in HCV genotype 1b (89.2%) and 2a (91.7%). As a result of apoE genotyping, we confirmed an association with HCV infection and the apoE ε3 allele. However, the ratios of the apoE ε3 allele among the patients with genotype 1b and 2a were similar to each other.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Apolipoprotein A5 3'-UTR variants and cardiometabolic traits in Koreans: results from the Korean genome and epidemiology study and the Korea National Health and Nutrition Examination Survey

BACKGROUND/OBJECTIVES: This study aimed to test the association between APOA5 3'-UTR variants (rs662799) and cardiometabolic traits in Koreans. SUBJECTS/METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained. APOA5 mRNA expression was also measured. RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports. In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes. Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [β = −2.048, P < 0.001; β = −2.199, P < 0.001] as well as elevation of circulating triglyceride levels [β = 0.053, P < 0.001; β = 0.066, P < 0.001] in both the KoGES-ASAS and KNHANES groups. In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = −0.277, P = 0.027) and circulating triglyceride level (r = −0.340, P = 0.006) but not significantly correlated with circulating HDL cholesterol level. On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms. CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES. The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.

Detection of Familial Hypercholesterolemia Using Next Generation Sequencing in Two Population-Based Cohorts / 전남의대학술지

We aimed to evaluate the prevalence of familial hypercholesterolaemia (FH) in a subject with hypercholesterolaemia from two population-based cohorts in South Korea. A total of 283 subjects with total cholesterol levels of 290 mg/dL (7.5 mmol/L) or higher were selected from the Namwon and Dong-gu Studies. We used next generation sequencing (NGS) to detect mutations in low-density lipoprotein receptors (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. We have confirmed 17 different mutations of the LDLR, APOB and PCSK9 in 23 subjects (8.1%). Eleven LDLR variants and one APOB variant have been previously reported. One LDLR and two PCSK9 rare variants were identified in the variants database, but not in the FH mutation database. Two novel LDLR variants were found, p.Leu680Val, and p.Thr734Phe. No LDLR, APOB or PCSK9 deletions nor insertions were found. When the subjects were restricted to 110 subjects with a total cholesterol ≥310 mg/dL, only 10 variants were found in the 10 subjects (9.1%). These results suggest that given the low prevalence of FH mutations in subjects with high total cholesterol levels, NGS-based testing for a population-based approach to FH detection may not be cost-effective.

Lack of Evidence of the Role of APOA5 3’UTR Polymorphisms in Iranian Children and Adolescents with Metabolic Syndrome

BACKGROUND: Metabolic syndrome (MetS) is a complex and multifactorial disorder characterized by insulin resistance, dyslipidaemia, hyperglycemia, abdominal obesity, and elevated blood pressure. The apolipoprotein A5 (APOA5) gene variants have been reported to correlate with two major components of MetS, including low levels of high density lipoprotein cholesterol (HDL-C) and high levels of triglyceride. In the present study, we explored the associations between five single nucleotide polymorphisms (SNPs) of APOA5 gene and the MetS risk. METHODS: In a case-control design, 120 Iranian children and adolescents with/without MetS were genotyped by polymerase chain reaction-sequencing for these SNPs. Then, we investigated the association of SNPs, individually or in haplotype constructs, with MetS risk. RESULTS: The rs34089864 variant and H1 haplotype (harboring the two major alleles of rs619054 and rs34089864) were associated with HDL-C levels. However, there was no significant association between different haplotypes/individual SNPs and MetS risk. CONCLUSION: These results presented no association of APOA5 3’UTR SNPs with MetS. Further studies, including other polymorphisms, are required to investigate the involvement of APOA5 gene in the genetic susceptibility to MetS in the pediatric age group.

Predictors of Institutionalization in Patients with Alzheimer's Disease in South Korea

BACKGROUND AND PURPOSE: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00–1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06–1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20–2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.