Disorder Of Lipoprotein Metabolism Research Articles

Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (-57.0 ± 2.6% to -83.9 ± 1.6%) and cholesterol (-35.3 ± 4.4% to -60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (-41.5 ± 3.7% to -97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.

The Role of Advanced Glycation End Products on Dyslipidemia.

Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs' production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.

Comparing translational success rates across medical research fields - A combined analysis of literature and clinical trial data.

Many interventions that show promising results in preclinical development do not pass clinical tests. Part of this may be explained by poor animal-to-human translation. Using animal models with low predictability for humans is neither ethical nor efficient. If translational success shows variation between medical research fields, analyses of common practices in these fields could identify factors contributing to successful translation. We assessed translational success rates in medical research fields using two approaches: through literature and clinical trial registers. Literature: We comprehensively searched PubMed for pharmacology, neuroscience, cancer research, animal models, clinical trials, and translation. After screening, 117 review papers were included in this scoping review. Translational success rates were not different within pharmacology (72%), neuroscience (62%), and cancer research (69%). Clinical trials: The fraction of phase-2 clinical trials with a positive outcome was used as a proxy (i.e., an indirect resemblance measure) for translational success. Trials were retrieved from the WHO trial register and categorized into medical research fields following the international classification of disease (ICD-10). Of the phase-2 trials analyzed, 65.2% were successful. Fields with the highest success rates were disorders of lipoprotein metabolism (86.0%) and epilepsy (85.0%). Fields with the lowest success rates were schizophrenia (45.4%) and pancreatic cancer (46.0%). Our combined analyses suggest relevant differences in success rates between medical research fields. Based on the clinical trials, comparisons of practice, e.g., between epilepsy and schizophrenia, might identify factors that influence translational success.

Xanthoma in different species - an unusual tumor with many faces.

Xanthoma is an interesting, inflammatory, noncancerous lesion that is rarely diagnosed in companion animals, although it has been reported in a number of domestic and wild species. Macroscopically, it can range from a few millimeter plaques or nodules to even several-centimeter masses. It usually occurs within the skin, but has been diagnosed in almost all other internal systems and organs. As the name suggests, xanthoma most often is of yellow color, but whitish and red forms are also encountered. Although inconspicuous, the presence of xanthoma is often reflected in disorders of lipid and lipoprotein metabolism, which affects the entire body. Therefore, in patients with even a small xanthoma on the skin, coexisting metabolic and endocrine disorders should be excluded, such as: hyperlipidemia, hypercholesterolaemia, hypothyroidism, hyperadrenocorticism and diabetes.

Inherited Lipid Disorders in Children: Experience from a Tertiary Care Centre.

Primary dyslipidaemia in children is a rare inherited disorder of lipoprotein metabolism with debilitating sequelae and poor outcomes. Lipid-lowering drugs have less often been used in children and long-term outcome studies are scarce. The purpose of this study was to understand the clinical and laboratory profile, response to treatment on follow up and outcome of primary dyslipidaemia in Indian children. Clinical records, including historical details, examination features and laboratory and radiological evaluation of children diagnosed with primary dyslipidaemia, presenting over the last 9 years were studied. Cascade screening was done for family members of the patients to detect dyslipidaemia in parents and siblings. All children were followed up 3 to 6 monthly for clinical and laboratory evaluation. Diet and drug therapy, initiated as appropriate, were modified as necessary. Of nine children with primary dyslipidaemia, seen over the last 9 years, homozygous familial hypercholesterolaemia (HoFH) (n = 4/9), familial hypertriglyceridaemia (FHT) (n = 3/9), familial combined hyperlipidemia (FCH) (n = 1/9), mutation proven chylomicronaemia syndrome (n = 1/9) were the phenotypes seen. Multiple xanthomas (n = 4/9), recurrent pancreatitis (n = 2/9) and incidentally found biochemical abnormality (n = 3/9) were the chief presenting features. Medical nutrition therapy and lipid-lowering drugs, as appropriate, were instituted in all. Follow-up over 16 months (range 4 to 90 months) revealed no deaths and no new onset of symptoms. Atherosclerotic plaques in the carotid artery were seen in one child, who presented late, despite fair compliance to treatment. Interestingly, lipid levels decreased in all cases and were normalised in two. Primary dyslipidaemia when detected early and treated aggressively can improve short-term outcomes.

Current status of post-traumatic injury with acute gastrointestinal injury and progress in diagnosis and treatment

Hypertriglyceridemia is the third most common cause of acute pancreatitis worldwide, and in China, it is the second leading cause. It mainly affects patients with underlying lipoprotein metabolism disorders and comorbidities like diabetes mellitus, alcohol abuse, or drug use. Pancreatitis caused by hypertriglyceridemia has similar clinical manifestations to acute pancreatitis caused by other factors but has a longer course and more complications, increasing the likelihood of organ failure. Treatment involves aggressive fluid resuscitation, pain control, and nutritional support, similar to acute pancreatitis from other causes. Timely recognition of hypertriglyceridemia is crucial for proper management, preventing recurrence, and long-term disease management.

Counseling couples at risk of having a child with homozygous familial hypercholesterolemia – Clinical experience and recommendations

Homozygous familial hypercholesterolemia (HoFH) is a rare, potentially life-limiting, inherited disorder of lipoprotein metabolism characterized by extremely high low-density lipoprotein cholesterol levels. When both parents have heterozygous FH, there is a 25% chance they will conceive a child with HoFH. Here we describe our clinical experience with two such prospective parent couples who were counseled regarding reproductive options and prenatal testing for HoFH. These cases showcase how, in consultation with a molecular geneticist and pediatric cardiologist, parents may be informed of the prognosis and treatment outlook of HoFH based on the FH-variants carried, to ultimately make personal decisions on reproductive options. One couple opted for prenatal testing and termination of pregnancy in case HoFH was found, while the other accepted the risk without testing. We review the available literature on preconception counseling for HoFH and provide practical guidance to clinicians counseling at-risk couples. Optimal counseling of prospective parents may help prevent future physical and psychological problems for both parent and child.

Associations Among Multimorbid Conditions in Hospitalized Middle-aged and Older Adults in China: Statistical Analysis of Medical Records.

Multimorbidity has become a new challenge for medical systems and public health policy. Understanding the patterns of and associations among multimorbid conditions should be given priority. It may assist with the early detection of multimorbidity and thus improve quality of life in older adults. This study aims to comprehensively analyze and compare associations among multimorbid conditions by age and sex in a large number of middle-aged and older Chinese adults. Data from the home pages of inpatient medical records in the Shenzhen National Health Information Platform were evaluated. From January 1, 2017, to December 31, 2018, inpatients aged 50 years and older who had been diagnosed with at least one of 40 conditions were included in this study. Their demographic characteristics (age and sex) and inpatient diagnoses were extracted. Association rule mining, Chi-square tests, and decision tree analyses were combined to identify associations between multiple chronic conditions. In total, 306,264 hospitalized cases with available information on related chronic conditions were included in this study. The prevalence of multimorbidity in the overall population was 76.46%. The combined results of the 3 analyses showed that, in patients aged 50 years to 64 years, lipoprotein metabolism disorder tended to be comorbid with multiple chronic conditions. Gout and lipoprotein metabolism disorder had the strongest association. Among patients aged 65 years or older, there were strong associations between cerebrovascular disease, heart disease, lipoprotein metabolism disorder, and peripheral vascular disease. The strongest associations were observed between senile cataract and glaucoma in men and women. In particular, the association between osteoporosis and malignant tumor was only observed in middle-aged and older men, while the association between anemia and chronic kidney disease was only observed in older women. Multimorbidity was prevalent among middle-aged and older Chinese individuals. The results of this comprehensive analysis of 4 age-sex subgroups suggested that associations between particular conditions within the sex and age groups occurred more frequently than expected by random chance. This provides evidence for further research on disease clusters and for health care providers to develop different strategies based on age and sex to improve the early identification and treatment of multimorbidity.

Alteration in Redox Status and Lipoprotein Profile in COVID-19 Patients with Mild, Moderate, and Severe Pneumonia.

Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.

Causal associations between disorders of lipoprotein metabolism and ten cardiovascular diseases.

Disorders of lipoprotein metabolism have been linked with an increased risk of cardiovascular diseases (CVDs) but the causal association is unclear. In this study, we investigated the causal association between disorders of lipoprotein metabolism and CVDs using two-sample Mendelian randomization (MR). The exposure was obtained from Finn genome-wide association studies (14,010 cases, 197,259 controls), and the corresponding CVDs were extracted from the largest published genome-wide association studies. A random-effects inverse-variance weighted method was used for the main analyses with a complementary analysis using the weighted median and MR-Egger approaches. Multiple sensitivity analyses were performed to assess horizontal pleiotropy. The MR analysis indicated positive associations of disorders of lipoprotein metabolism with coronary artery disease (odds ratio [OR] 1.670, 95% confidence interval [CI] 1.373–2.031; p < 0.001), aortic aneurysm (OR 1.394, 95% CI 1.199–1.619; p < 0.001), heart failure (OR 1.20, 95% CI 1.115–1.294; p < 0.001), hypertension (OR 1.011, 95% CI 1.006–1.091; p < 0.001), old myocardial infarction (OR 1.004, 95% CI 1.002–1.007; p = 0.001), and stroke (OR 1.002, 95% CI 1.001–1.003; p = 0.002). There is a suggestive causal relationship between disorders of lipoprotein metabolism and atrial fibrillation (OR 1.047, 95% CI 1.006–1.091; p = 0.026) and acute myocardial infarction (OR 1.003, 95% CI 1.001–1.005; p = 0.012). There was limited evidence of a causal association between disorders of lipoprotein metabolism and peripheral vascular disease and venous thromboembolism. Our findings indicate a significant causal association between disorders of lipoprotein metabolism and many CVDs, including coronary artery disease, aortic aneurysm, heart failure, hypertension, old myocardial infarction, and stroke. These associations may be useful for development of treatment strategies that regulate lipoprotein metabolism in patients with CVD.

Structure Of Comorbidity In Urban Population With Essential Hypertension In The Clinical Practice Of A Local General Practitioner

Taking into account gender- and age-related features, to examine the structure of comorbidity in outpatients with essential hypertension residing in the city of Tambov. Material and Methods — This research was an observational cross-sectional study based on data extracted from 47,113 electronic medical records (EMRs) of patients 20-99 years of age residing in Tambov. The study included 29,282 (62.2%) women and 17831 (37.8%) men. Results — Essential hypertension is habitually associated with osteochondrosis (41.5% of patients with hypertension), cerebrovascular diseases (35.1%), arthrosis (28.3%), ischemic heart disease (IHD) (28.7%), menopausal disorders (17.5%), pancreatic diseases (15.4%), diabetes mellitus (14.7%), benign mammary dysplasia (14.2%), retinal diseases (12.9%), disorders of lipoprotein metabolism (12.4%), senile cataract (10.6%), gastritis and duodenitis (10.7%), varicose veins (10.1%), and thyroid diseases (10.0%). IHD is more common among men with hypertension, while other comorbidities are more characteristic for women. The most striking gender-related difference was associated with the finding that women with hypertension had varicose veins as a comorbidity (RR=1.398; 95% CI 1.376-1.422), while the smallest difference between genders related to retinal diseases (RR=1.065; 95% CI 1.038-1.092). IHD was strongly associated with the male gender (RR=1.101; 95% CI 1.056-1.148). Three diseases were more often associated with hypertension in the age range of 80-89 years (cerebrovascular disease, IHD, osteochondrosis); some of the diseases had the highest incidence in the age range of 60-69 years, and other disorders occurred in the age range of 40-59 years. Conclusion — The gender- and age-related features of comorbid pathology associated with essential hypertension among urban residents revealed in this study are extremely important in the clinical practice of a local general practitioner for developing optimal patient-oriented treatment plans.

Pharmacoeconomic rationale for the treatment of lipoprotein metabolism disorders in older people

In order to preserve the health of elderly patients, methodological approach- es to the pharmacoeconomic substantiation of the inclusion of drugs for the treatment of dyslipidemia in the list of vital and essential drugs (EDL) were adapted and an appropriate assessment of the drug of cholesterol absorption inhibition was carried out, which showed that from the point of view of the healthcare system, the presence of this drug in the list will have a positive effect: Impact on the budget by increasing the availability of this drug for patients and delaying the prescription of expensive drugs of the PCSK9 inhibitor class. From a clinical point of view, increasing the availability of cholesterol absorption inhibition drugs for patients when it is included in the list of essential drugs will ensure that the correct sequence of the therapeutic line is followed in the treatment of dyslipidemia.

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study.

Background and aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH. Results: This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0–65.5) years, with a median treatment duration of 31.0 (IQR 14.0–40.5) months. At baseline, four (44.4%) patients had hypertension, one (11.1%) had diabetes mellitus, two (22.2%) were active smokers, and five (55.5%) reported ASCVD. The baseline LDL-C was 257.0 (IQR, 165.3–309.2) mg/dL. All patients were on statins plus ezetimibe, three were receiving Lipoprotein apheresis (LA), and one was also receiving proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The addition of lomitapide (mean dose, 10 mg) resulted in the achievement of a median on-treatment LDL-C of 101.7 mg/dL (IQR, 71.3–138.3; 60.4% reduction from baseline), with a best LDL-C value of 68.0 mg/dL (IQR, 43.7–86.7; 73.5% reduction from baseline). During follow-up, one patient stopped both PCSK9i and LA. Recurrence of ASCVD events was reported in one patient. The median on-treatment aspartate transaminase and alanine transaminase values were 31.1 (IQR, 22.6–48.3) U/L and 31.1 (IQR, 27.2–53.8) U/L, respectively. Among six ARH patients with available fibroscan examination, liver stiffness values recorded at the last visit were within the normal range (median, 4.7 KPa; IQR, 3.6–5.3 KPa). Conclusion: Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.

Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon.

Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia.

Nutrition interventions for youth with dyslipidemia: a National Lipid Association clinical perspective

A heart-healthy lifestyle, beginning at an early age and sustained throughout life, may reduce risk for cardiovascular disease in youth. Among youth with moderate to severe dyslipidemia and/or those with familial hypercholesterolemia, lipid-lowering medications are often needed for primary prevention of cardiovascular disease. However, lifestyle interventions are a foundation for youth with dyslipidemia, as well as those without dyslipidemia. There are limited data supporting the use of dietary supplements in youth with dyslipidemia at this time. A family-centered approach and the support of a multi-disciplinary healthcare team, which includes a registered dietitian nutritionist to provide nutrition counseling, provides the best opportunity for primary prevention and improved outcomes. While there are numerous guidelines that address the general nutritional needs of youth, few address the unique needs of those with dyslipidemia. The goal of this National Lipid Association Clinical Perspective is to provide guidance for healthcare professionals caring for youth with disorders of lipid and lipoprotein metabolism, including nutritional guidance that complements the use of lipid lowering medications.

High-Density Lipoproteins: A Role in Inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high rates of disability and mortality. COPD is characterized by chronic inflammation in the bronchi as well as systemic inflammation, which contributes significantly to the clinically heterogeneous course of the disease. Lipid metabolism disorders are common in COPD, being a part of its pathogenesis. High-density lipoproteins (HDLs) are not only involved in lipid metabolism, but are also part of the organism’s immune and antioxidant defense. In addition, HDL is a versatile transport system for endogenous regulatory agents and is also involved in the removal of exogenous substances such as lipopolysaccharide. These functions, as well as information about lipoprotein metabolism disorders in COPD, allow a broader assessment of their role in the pathogenesis of heterogeneous and comorbid course of the disease.

Role of adenosine deaminase in dyslipidemia

Background and Objectives: Dyslipidemia is a family of lipoprotein metabolism disorders manifested by elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and reduced high density lipoprotein cholesterol (HDL-C) concentrations in the blood.[1] Dyslipidemia was defined according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III. Hypercholesterolemia was declared for participants with either a total cholesterol ˃ 200 mg/dL or an LDL cholesterol ˃ 130 mg/dL while HDL hypocholesterolemia was at HDL cholesterol ˂ 40 mg/dL. Hypertriglyceridemia was declared for triglyceride plasma level ˃ 150 mg/dL. A combination of hypercholesterolemia and hypertriglyceridemia was classified as mixed hyperlipidemia while atherogenic dyslipidemia was a combination of HDL hypocholesterolemia, hypertriglyceridemia and LDL hypercholesterolemia. Material and Methods : The study population included 100 subjects in which 50 were newly diagnosed patients of dyslipidemia and rest 50 healthy attending both outpatients and inpatients department Biochemistry of Rajshree Medical Research Institute Bareilly. Results: In our study we found the mean values of ADA, TC, HDL-C, LDL-C and TG in cases and controls respectively.

Diagnostic criteria of dyslipidemia with lipid fractions &amp;amp; its association with the risk of coronary heart disease: A review

Cardiovascular disease is the leading cause of illness and death across world widely. Lipid and lipoprotein metabolism disorder like dyslipidemia patients may prone to develop premature atherosclerosis. Types of dyslipidemia are hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia, and low levels of high-density lipoprotein cholesterol. Hypercholesterolemia can causes atherosclerosis and hypertriglyceridemia can consequence in pancreatitis. The laboratory findings are beneficial in the analysis and controlling of Dyslipidemia encompass assessment of serum cholesterol, serum triglycerides, serum high-density lipoprotein cholesterol, and serum low-density lipoprotein cholesterol by directly and through calculation. Laboratory investigation which are helpful to eliminate secondary causes of Dyslipidemia are assessment of TSH, Blood sugar levels, liver function test, serum creatinine, and plasma and urine protein level.

Risk of Dyslipidemia in Obese Young Adult Subjects as Measured by Various Obesity Indices

Background: Obesity is strongly associated with atherogenic dyslipidemia phenotype and is an independent risk factor of cardiovascular disease (CVD). Besides body mass index (BMI), there are various obesity indices, namely waist circumference (WC) to detect central obesity, and percentage of body fat (%BF) using bioimpedance analysis (BIA) to detect peripheral-central obesity. The aim of this study is to determine which obesity index is better in predicting dyslipidemia. Methods: This cross-sectional study involved 99 professionally active doctors working at tertiary hospital, from January to March 2021. Obesity was measured by obesity indices such as BMI, WC, and %BF using BIA. After that, the serum lipid profile was then measured. Dyslipidemia is a disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency that may be manifested by high total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and low high-density lipoprotein cholesterol (HDL) cholesterol. Results: Of the total 99 subjects, 49.5% were male, while 50.5% were female. The prevalence of obesity based on BMI, WC, and %BF using BIA was 57.6%, 74.8%, and 72.7%, respectively. Obesity based on BMI has 9.8 times the risk of having low HDL cholesterol levels (odds ratio (OR) = 9.814, 95% confidence interval (CI): 1.213 - 79.379) and 4.6 times of having high triglycerides levels (OR = 4.618, 95% CI: 1.240 - 17.204). Meanwhile, central obesity based on WC has 3.1 times the risk of having high LDL cholesterol levels (OR = 3.100, 95% CI: 1.170 - 8.218). On the contrary, the results of the analysis on obesity based on %BF on lipid profile were not significant. Conclusions: Obesity based on BMI and WC measurements are better than %BF in predicting dyslipidemia. J Endocrinol Metab. 2022;12(3):102-106 doi: https://doi.org/10.14740/jem819

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents.

Disorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the MIR499 gene—a microRNA previously linked to CVD—to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort, n = 125) and in patients treated with statins (STAT cohort, n = 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the MIR499, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the MIR499, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444 MIR499 SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies.