Increased Beef Consumption Increases Apolipoprotein A-I but Not Serum Cholesterol of Mildly Hypercholesterolemia Men with Different Levels of Habitual Beef Intake

2002 ◽  
Vol 227 (4) ◽  
pp. 266-275 ◽  
Author(s):  
Dana R. Smith ◽  
Randall Wood ◽  
Stephen Tseng ◽  
Stephen B. Smith
Keyword(s):  
Oleic Acid ◽  
Serum Cholesterol ◽  
Ldl Cholesterol ◽  
Treatment Time ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
The United States ◽  
Cholesterol Concentration ◽  
Apolipoprotein A ◽  
Lean Beef

The objective of this research was to compare the effects of a lean beef enriched in oleic acid to a beef that is typical of the commercial beef consumed in the United States. Ten mildly hypercholesterolemic men, ages 34-58 years old, were selected from the Texas A&M University faculty and staff. Subjects were randomly assigned to one of two diets for a 6-week duration followed by a crossover after a 4-week habitual diet washout period. Diets were consumed daily for a 6-week study period. Participants substituted lean beef obtained from Wagyu bullocks or commercial beef for the meat typically consumed. Total cholesterol, apolipoproteins A-I and B, triacylglycerols, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured in serum samples collected weekly. Beef type had no effect on any measured variable. There were no significant differences between baseline HDL or LDL cholesterol concentrations after the consumption of the beef test diets. Apolipoprotein A-I, serum glucose, and uric acid concentrations were elevated by the additional dietary beef. Analysis of records of customary diets indicated that one group consumed 160 g of beef daily, whereas the other group consumed only 26 g of beef daily. Therefore, post hoc analyses tested the habitual beef intake x treatment time interaction. LDL cholesterol concentration was markedly higher in the group with low habitual beef Intake (180 vs 144 mg/dl), and HDL cholesterol was slightly higher (44 vs 40 mg/dl; post-test values) than for the group with high habitual beef intake, but there were no habitual intake x time interactions for LDL or HDL cholesterol. Creatinine and blood urea nitrogen concentrations also were greater in the individuals habitually consuming less beef. This study had three important findings: i) a lean beef source enriched with oleic acid was no different from commercial beef in its effect on lipoprotein fractions; ii) neither previous level of beef intake nor baseline LDL cholesterol concentration influenced the serum cholesterol response to added dietary beef. which was negative; and iii) apolipoprotein A-I, but not HDL or LDL cholesterol, was sensitive to the additional dietary beef.

Platelet Aggregation and Plasma Lipoproteins in Alcoholics During Alcohol Withdrawal

1986 ◽  
Vol 55 (02) ◽  
pp. 173-177 ◽  
Author(s):  
K Desai ◽  
J S Owen ◽  
D T Wilson ◽  
R A Hutton
Keyword(s):  
Platelet Aggregation ◽  
Alcohol Withdrawal ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Plasma Lipoprotein ◽  
Cholesterol Concentration ◽  
Arachidonic Acid Content ◽  
Low Density

SummaryPlatelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol: HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.

scholarly journals Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer

2021 ◽  
Author(s):  
Masato Karayama ◽  
Naoki Inui ◽  
Yusuke Inoue ◽  
Katsuhiro Yoshimura ◽  
Kazutaka Mori ◽  
...  
Keyword(s):  
Serum Cholesterol ◽  
Serum Lipid ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Small Cell ◽  
Chain Fatty Acid ◽  
Small Cell Lung ◽  
Long Chain Fatty Acid ◽  
Long Chain

Abstract Background Lipids have immunomodulatory functions and the potential to affect cancer immunity. Methods The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. Results When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. Conclusions Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.

scholarly journals Evaluation of some biochemical changes in the serum of phensedyl addicts of Gaibandha District, Bangladesh

2014 ◽  
Vol 20 ◽  
pp. 57-65
Author(s):  
Md Rashidul Hasan ◽  
Parvez Hassan ◽  
Md Abdul Jalil Miah
Keyword(s):  
Serum Cholesterol ◽  
Biochemical Parameters ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Hdl Cholesterol ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
P Value

Context: Abuse of the drug, Phensedyl like any other drug might exert adverse effects on vital organs of th e h u m an body like liver, kidney and heart. Objectives: To determine the effects of Phensedyl intake on the serum biochemical parameters of the addicts in order to access for damages of vital human organs like liver, kidney and heart. Materials and Methods: Study population consisted of 127 male Phensedyl addicts within the ages of 18–55 years of defined criteria from Gaibandha district, a Northern part of Bangladesh, during July 2009 to December 2011. Fifty (50) non-drug dependent healthy men of matched age, height, and socioeconomic status were included as controls from the same community. Biochemical parameters analyzed were – Serum creatinine, SGOT, SGPT and Lipid profiles (total serum cholesterol (TC), Serum triglyceride (TG), serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol determined by semiautomatic biochemistry analyzer using commercially available kits Results: Abuse of Phensedyl appears not to hamper the normal renal and liver function in most of the addicts even after 8 years of Phensedyl intake irrespective of age except in case of 4 abusers. Serum total cholesterol (TC) remained almost unchanged among the addicts abusing Phensedyl for less than 8 years. But very strikingly, addicts taking Phensedyl for more than 8 years had higher trends in serum cholesterol i.e. more than 200 ml/dl. Of the addict’s, 44.36% abusing Phensedyl for less than 8 years had normal triglyceride (TG) values whereas, in 45.66% addicts abusing the drug for more than 8 years had clinically very significantly elevated triglyceride levels, which was also found to be statistically very significant (p value =0.0001), indicating the risk of developing cardiac diseases. Of the total addicts 53.53% had low levels of HDL cholesterol, which is clinically and statistically found to be very significant (p value =0.002). Of the addict’s 43% taking the drug for less than 8 years had normal LDL levels but significantly elevated values were recorded in 34% of the abusers who had been taking the drug for more than 8 years. Conclusion: Long time (> 8 years) Phensedyl abusers are at the high risk of developing Brain stroke, Coronary Heart Disease (CHD), Ischemic stroke or transient ischemic attack (TIA) as there is the triad of: Elevated LDL cholesterol, Low HDL cholesterol and elevated Triglyceride. DOI: http://dx.doi.org/10.3329/jbs.v20i0.17656 J. bio-sci. 20: 57-65, 2012

Abstract 492: Atherogenic Dyslipidemia in Patients with Transient Ischemic Attack

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hye-Yeon Choi
Keyword(s):  
Transient Ischemic Attack ◽  
Ldl Cholesterol ◽  
Recurrent Stroke ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Vascular Lesion ◽  
Vascular Lesions ◽  
Cholesterol Concentration ◽  
Atherogenic Dyslipidemia ◽  
Ischemic Attack

Background: The risk of recurrent stroke following transient ischemic attack (TIA) is reported up to 15% at 90 days after the attack. Urgent assessment and combined use of preventive treatments in appropriate patients can reduce this risk significantly. The atherogenic dyslipidemia in patients with TIA may be associated with intracranial artery stenosis and higher risk of early recurrent stroke. This study was aimed to investigate if dyslipidemia was related to atherosclerotic vascular lesions in the TIA patients. Methods: Patients with TIA who admitted to single hospital were included. TIA was defined as an acute loss of focal cerebral function, lasting fewer than 24 hours. If brain magnetic resonance imaging scans showed acute infarction, the patient was judged to have a TIA with a new lesion; if not, the event was classified as TIA without a new lesion. Radiologic findings were reviewed retrospectively. Association between presence of atherosclerotic vascular lesions and lipid profile were examined. Atherogenic dyslipidemia was defined as high density lipoprotein (HDL) cholesterol ≤ 40 mg/dL and triglycerides ≥ 150 mg/dL. Level of non-HDL cholesterol was calculated as total cholesterol concentration minus HDL cholesterol concentration. Presence of classic risk factors of atherosclerosis and vascular disease were also reviewed. Results: Among 117 TIA patients, 106 patients who had available results were included to the analysis. Mean age was 64 years (± 13), and 48 were men (42.1%). Atherosclerotic vascular lesion was shown in 56 patients (52.8%). Presence of atherosclerotic vascular lesions was associated with age, diabetes, low density lipoprotein (LDL) cholesterol concentrations, and level of CRP. Atherogenic dyslipidemia was not related to vascular lesions. Among 106 patients, only 18 patients (17.0%) were diagnosed as TIA with a new lesion. Presence of acute cerebral infarction was associated with presence of atherosclerosis. Diabetes and current smoking were associated with new ischemic lesion related TIA. Conclusions: In TIA patients, concentrations of LDL cholesterol were related atherosclerotic vascular lesion which is known to be associated with recurrent stroke after TIA. It might be helpful to screen high risk TIA patient.

Exclusive Breast-Feeding and Weaning: Effect on Serum Cholesterol and Lipoprotein Concentrations in Infants During the First Year of Life

PEDIATRICS ◽  
1992 ◽  
Vol 89 (4) ◽  
pp. 663-666
Author(s):  
Markku J. T. Kallio ◽  
Leena Salmenperä ◽  
Martti A. Siimes ◽  
Jaakko Perheentupa ◽  
Tatu A. Miettinen
Keyword(s):  
Breast Feeding ◽  
Serum Cholesterol ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Mean Difference ◽  
Cholesterol Concentration ◽  
Total Serum ◽  
Apoprotein B ◽  
The Mean ◽  
Breast Fed

The total serum cholesterol concentration of infants was investigated at birth (n = 193) and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n= 188), and 12 months (n = 196). Concentrations of cholesterol—very-low-density lipoprotein (VLDL), low-density lipoprotein(LDL), high-density lipoprotein-2 (HDL2), HDL3—and apoprotein B were analyzed in 36 infants at 2, 6, 9, and 12 months of age. Serum cholesterol concentration rose significantly more slowly in the weaned infants compared with exclusively breast-fed infants. The mean difference in total serum cholesterol value between the exclusively breast-fed and weaned infants was largest at ages 2 (0.9 mmol/L, P &lt; .001), 4 (0.6 mmol/L, P &lt; .01), and 6 months (0.5 mmol/L, P &lt; .01). The LDL cholesterol concentration was lower in weaned infants compared with exclusively breast-fed infants at age 2 and 6 months; the mean difference in LDL cholesterol value was 0.9 mmol/L at age 2 months (P &lt; .001)and 0.7 mmol/L at age 6 months (P &lt; .025). Also, the apoprotein B concentration was lower in weaned infants; the mean difference was 24 mg/dL at age 2 months (P &lt; .01) and 30 mg/dL at age 6 months (P&lt; .05). The apoprotein B-LDL cholesterol ratio was stable and similar in both feeding groups through the year. The HDL2 cholesterol concentration was lower in the formula-fed than in breast-fed infants at 2 months of age while the VLDL and HDL3 cholesterol concentrations were independent of the diet. The HDL-LDL cholesterol ratio was higher in formula-fed compared with breast fed infants at 2 and 6 months of age. Thus,low intake of cholesterol and high intake of unsaturated fatty acids modify blood lipid pattern markedly in infancy. Breast-feeding is the natural method of feeding an infant and the cholesterol level with breast-feeding must be considered physiological, so it is to be asked whether artificially made formulas in this respect are sufficient at the moment.

Inverse Relationship in Jamaica between Plasma High-Density Lipoprotein Cholesterol Concentration and Coronary-Disease Risk as Predicted by Multiple Risk-Factor Status

1976 ◽  
Vol 51 (5) ◽  
pp. 475-482 ◽  
Author(s):  
G. J. Miller ◽  
N. E. Miller ◽  
M. T. Ashcroft
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Concentration ◽  
Multiple Risk Factor ◽  
Coronary Risk ◽  
Plasma High Density ◽  
Risk Factor Status

1. The relation between plasma high-density lipoprotein (HDL) cholesterol concentration and multiple coronary-risk factor status has been assessed in fifty-two middle-aged clinically healthy men from urban and rural Jamaica. 2. Rural hill-farmers had a superior exercise performance (assessed by the responses to submaximal test exercise), less body fat, and lower fasting levels for plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, total triglyceride and blood glucose than urban businessmen. Mean plasma HDL cholesterol was considerably higher in farmers then businessmen. 3. Multilinear regression analysis showed HDL cholesterol concentration to be independently and inversely correlated with plasma triglyceride, LDL cholesterol and diastolic blood pressure and that these relationships applied across the urban and rural sub-groups. There was also some evidence that HDL cholesterol concentration increased with stature. When these factors were taken into account, age, ethnic group, adiposity, weight, exercise performance, smoking history and blood glucose made no further significant contribution to the prediction of HDL cholesterol concentration. 4. Thus plasma HDL cholesterol concentration was highest in those subjects with the lowest coronary-risk as predicted by their multiple risk-factor status, an observation which supported other evidence that coronary-risk is inversely related to plasma HDL concentration. 5. The results raise the possibility that coronary-risk can be more simply estimated from the plasma HDL cholesterol concentration than from a consideration of other major lipid risk factors and blood pressure.

scholarly journals NIGELLA SATIVA (KALONJI)

2011 ◽  
Vol 18 (01) ◽  
pp. 142-146
Author(s):  
MUHAMMAD ANWAR BURIRO ◽  
MUHAMMAD TAYYAB ◽  
ALLAH DITTA
Keyword(s):  
Serum Cholesterol ◽  
Ldl Cholesterol ◽  
Nigella Sativa ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Total Serum ◽  
Control Group ◽  
Total Serum Cholesterol ◽  
Blood Samples ◽  
Cholesterol Levels

The increased level of LDL-c in the serum has a high risk and the increased serum HDL-c level has a low risk for the development of atherosclerosis. The effect of Nigella Sativa on levels of cholesterol fractions were determined in this study on rats. Methods: 24 albino rats of 08 weeks age having equal number of males and females were kept at optimum atmospheric condition. The blood samples were taken at the start and different control and experimental diets were given for 24 weeks. The experimental diets were added with Nigella Sativa as 30 mg/kg body weight. The blood samples were taken at the end of study. The blood samples drawn at the start and end of the study were estimated for serum cholesterol. The results of control and experimental groups were compared. Results: Total serum cholesterol in the control group showed increase from 8.3±3.30 to 13.96±9.3 at 24 weeks. The serum HDL cholesterol showed increase from 44.4±6.12 to 80.45±5.95 level at 24 weeks. The serum LDL cholesterol showed increase from 8.3±3.30 to 13.96±9.3 at 24 weeks. The total serum cholesterol in experimental group was increased from 76.9±6.5 to 117.5± 6.65 at 24 weeks. The serum HDL cholesterol levels was increased from 41.7±4.9 to 83.42±5.92 at 24 weeks as compared with control group. The LDL cholesterol levels were decreased from 12.7±6.9 to 8.5±7.8 at 24 weeks. Conclusions: This study shows significant decrease in serum low density lipoprotein cholesterol level, and increase in serum high density lipoprotein cholesterol levels.

Antibody titer against malondialdehyde-modified LDL compares with HDL cholesterol concentration in identifying angiographically verified coronary artery disease. Comparison of tests by ROC analysis

2005 ◽  
Vol 43 (4) ◽  
Author(s):  
Riikka Rontu ◽  
Saara Metso ◽  
Olli Jaakkola ◽  
Matti Nikkilä ◽  
Hannu Jokela ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antibody Titer ◽  
Roc Analysis ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Concentration ◽  
Modified Ldl ◽  
Artery Disease

AbstractAntibody titer against malondialdehyde (MDA)-modified low-density lipoprotein (LDL) has been found to be associated with atherosclerosis, but it has not been established whether it would detect subjects with coronary artery disease (CAD). In the present study, receiver-operating characteristic (ROC) analysis was used to compare the diagnostic accuracy of the antibody titer against MDA-modified LDL and high-density lipoprotein (HDL) and LDL cholesterol levels in discrimination between subjects with (n=51) and without (n=35) angiographically verified 3-vessel CAD. As a result, the antibody titer against MDA-modified LDL was lower in subjects with CAD compared with subjects without CAD (p<0.0001). The area under the ROC plot was 0.822 (95% CI, 0.727 to 0.918) for the antibody titer and 0.769 (95% CI, 0.661 to 0.876) for the HDL cholesterol concentration. Both the antibody titer and the plasma HDL cholesterol level were more accurate markers of CAD than the LDL cholesterol level. As a conclusion, our results indicate that the antibody titer against MDA-modified LDL discriminates between subjects with widespread CAD and those without CAD similarly as the HDL cholesterol concentration. Moreover, the antibody titer against MDA-modified LDL is inversely correlated with the risk of severe CAD.

Risk factors for cardiovascular diseases and development of prehypertension

2018 ◽  
pp. 37-43
Author(s):  
В.В. Шерстнев ◽  
М.А. Грудень ◽  
В.П. Карлина ◽  
В.М. Рыжов ◽  
А.В. Кузнецова ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
Left Ventricular ◽  
Optimal Blood Pressure

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.

Identification of six novel susceptibility loci for dyslipidemia by longitudinal exome-wide association studies in Japanese

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oguri ◽  
K Kato ◽  
H Horibe ◽  
T Fujimaki ◽  
J Sakuma ◽  
...  
Keyword(s):  
Serum Lipid ◽  
Ldl Cholesterol ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Cross Sectional ◽  
Genome Wide

Abstract Background The circulating concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, and low density lipoprotein (LDL)-cholesterol have a substantial genetic component. Although previous genome-wide association studies identified various genes and loci related to plasma lipid levels, those studies were conducted in a cross-sectional manner. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to hypertriglyceridemia, hypo-HDL-cholesterolemia, and hyper-LDL-cholesterolemia in Japanese. We have now performed longitudinal exome-wide association studies (EWASs) to identify novel loci for dyslipidemia by examining temporal changes in serum lipid profiles. Methods Longitudinal EWASs (mean follow-up period, 5 years) for hypertriglyceridemia (2056 case, 3966 controls), hypo-HDL-cholesterolemia (698 cases, 5324 controls), and hyper-LDL-cholesterolemia (2769 cases, 3251 controls) were performed with Illumina Human Exome arrays. The relation of genotypes of 24,691 single nucleotide polymorphisms (SNPs) that passed quality control to dyslipidemia-related traits was examined with the generalized estimating equation (GEE). To compensate for multiple comparisons of genotypes with each of the three conditions, we applied Bonferroni's correction for statistical significance of association. Replication studies with cross-sectional data were performed for hypertriglyceridemia (2685 cases, 4703 controls), hypo-HDL-cholesterolemia (1947 cases, 6146 controls), and hyper-LDL-cholesterolemia (1719 cases, 5833 controls). Results Longitudinal EWASs revealed that 30 SNPs were significantly (P&lt;2.03 × 10–6 by GEE) associated with hypertriglyceridemia, 46 SNPs with hypo-HDL-cholesterolemia, and 25 SNPs with hyper-LDL-cholesterolemia. After examination of the relation of identified SNPs to serum lipid profiles, linkage disequilibrium, and results of the previous genome-wide association studies, we newly identified rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25 as a susceptibility loci for hypo-HDL-cholesterolemia; and rs34902660 of SLC17A3 and rs1042127 of CDSN for hyper-LDL-cholesterolemia. These SNPs were not in linkage disequilibrium with those previously reported to be associated with dyslipidemia, indicating independent effects of the SNPs identified in the present study on serum concentrations of HDL-cholesterol or LDL-cholesterol in Japanese. According to allele frequency data from the 1000 Genomes project database, five of the six identified SNPs were monomorphic or rare variants in European populations. In the replication study, all six SNPs were associated with dyslipidemia-related phenotypes. Conclusion We have thus identified six novel loci that confer susceptibility to hypo-HDL-cholesterolemia or hyper-LDL-cholesterolemia. Determination of genotypes for these SNPs at these loci may prove informative for assessment of the genetic risk for dyslipidemia in Japanese. Funding Acknowledgement Type of funding source: None

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