scholarly journals Phosphorylation-related SNPs influence lipid levels and rheumatoid arthritis risk by altering gene expression and plasma protein levels

Rheumatology ◽  
2019 ◽  
Vol 59 (4) ◽  
pp. 889-898
Author(s):  
Xingbo Mo ◽  
Yufan Guo ◽  
Qiyu Qian ◽  
Mengzhen Fu ◽  
Huan Zhang
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Lipid Levels ◽  
Low Density Lipoprotein Cholesterol ◽  
Protein Levels

Abstract Objectives Phosphorylation-related single-nucleotide polymorphisms (phosSNPs) are missense SNPs that may influence protein phosphorylation. The aim of this study was to evaluate the effect of phosSNPs on lipid levels and RA. Methods We examined the association of phosSNPs with lipid levels and RA in large-scale genome-wide association studies (GWAS) and performed random sampling and fgwas analyses to determine whether the phosSNPs associated with lipid levels and RA were significantly enriched. Furthermore, we performed QTL analysis and Mendelian randomization analysis to obtain additional evidence to be associated with the identified phosSNPs and genes. Results We found 483 phosSNPs for lipid levels and 243 phosSNPs for RA in the GWAS loci (P < 1.0 × 10−5). SNPs associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, Total cholesterol (TC) and RA were significantly enriched with phosSNPs. Almost all of the identified phosSNPs showed expression quantitative trait loci (eQTL) effects. A total of 48 protein QTLs and 9 metabolite QTLs were found. The phosSNP rs3184504 (p.Trp262Arg) at SH2B3 was significantly associated with RA, SH2B3 expression level, and plasma levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC, hypoxanthine and 80 proteins, including beta-2-microglobulin. SH2B3 was differentially expressed between RA cases and controls in peripheral blood mononuclear cells and synovial tissues. Mendelian randomization analysis showed that SH2B3 expression level was significantly associated with TC level and RA. Plasma beta-2-microglobulin level was causally associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC levels and RA. Conclusion The findings suggested that phosSNPs may play important roles in lipid metabolism and the pathological mechanisms of RA. PhosSNPs may influence lipid levels and RA risk by altering gene expression and plasma protein levels.

The Effects of Low-Density Lipoprotein and High-Density Lipoprotein on Blood Viscosity Correlate with their Association with Risk of Atherosclerosis in Humans

1997 ◽  
Vol 92 (5) ◽  
pp. 473-479 ◽  
Author(s):  
Gregory D. Sloop ◽  
David W. Garber
Keyword(s):  
High Density Lipoprotein ◽  
Total Cholesterol ◽  
High Density Lipoprotein Cholesterol ◽  
Blood Viscosity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

1. Increased blood or plasma viscosity has been observed in almost all conditions associated with accelerated atherosclerosis. Cognizant of the enlarging body of evidence implicating increased viscosity in atherogenesis, we hypothesize that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis. 2. Blood viscometry was performed on samples from 28 healthy, non-fasting adult volunteers using a capillary viscometer. Data were correlated with haematocrit, fibrinogen, serum viscosity, total cholesterol, high-density lipoprotein-cholesterol, triglycerides and calculated low-density lipoprotein-cholesterol. 3. Low-density lipoprotein-cholesterol was more strongly correlated with blood viscosity than was total cholesterol (r = 0.4149, P = 0.0281, compared with r = 0.2790, P = 0.1505). High-density lipoprotein-cholesterol levels were inversely associated with blood viscosity (r = −0.4018, P = 0.0341). 4. To confirm these effects, viscometry was performed on erythrocytes, suspended in saline, which had been incubated in plasma of various low-density lipoprotein/high-density lipoprotein ratios. Viscosity correlated directly with low-density lipoprotein/high-density lipoprotein ratio (n = 23, r = 0.8561, P < 0.01). 5. Low-density lipoprotein receptor occupancy data suggests that these effects on viscosity are mediated by erythrocyte aggregation. 6. These results demonstrate that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity in healthy subjects correlate with their association with risk of atherosclerosis. These effects on viscosity may play a role in atherogenesis by modulating the dwell or residence time of atherogenic particles in the vicinity of the endothelium.

scholarly journals Kliničke i biokemijske značajke pretilosti u pacijenata sa shizofrenijom

2020 ◽  
Vol 56 (2) ◽  
pp. 166-177
Author(s):  
Sergej Nadalin ◽  
Jelena Rebić ◽  
Alena Buretić-Tomljanović ◽  
Dalibor Karlović ◽  
Vjekoslav Peitl ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Syndrome Scale ◽  
Negative Syndrome

Cilj: Istražili smo povezanost pojave pretilosti s kliničkim značajkama shizofrenije, poput dobi, trajanja bolesti, dobi nastupa bolesti, ovisnosti o pušenju i težine simptoma ocjenske ljestvice PANSS-a (engl. Positive and Negative Syndrome Scale – PANSS). Također smo testirali doprinos pretilosti biokemijskim parametrima: koncentracijama ukupnog kolesterola, LDL kolesterola (engl. low density lipoprotein cholesterol), HDL kolesterola (engl. high density lipoprotein cholesterol), triglicerida i glukoze u plazmi. Ispitanici i metode: U istraživanju su sudjelovala 142 kronična pacijenta sa shizofrenijom. Pretilim pacijentima smatrani su oni s vrijednostima indeksa tjelesne mase (ITM) &gt; 30, dok su pacijenti s normalnom tjelesnom masom (ITM: 20 – 25) i pacijenti s prekomjernom tjelesnom masom (ITM: 25 – 30) klasificirani u nepretile. Rezultati: Nije uočena statistički značajna povezanost pretilosti s kliničkim značajkama (P &gt; 0,05). Koncentracije ukupnog kolesterola i LDL kolesterola bile su značajno više u pretilih pacijentica u odnosu na nepretile pacijentice, dok su značajno više vrijednosti triglicerida uočene kod pretilih u odnosu na nepretile ispitanike oba spola (P &lt; 0,05). Ipak, samo se trajanje bolesti pokazalo značajnim prediktorom vrijednosti triglicerida u pacijentica, dok je učinak pretilosti ostao izvan statističke značajnosti (P &gt; 0.05). Pojava pretilosti opisuje približno 8,3 % varijabilnosti koncentracija triglicerida u muškaraca te 9,6 % i 13,8 % varijabilnosti koncentracija ukupnog kolesterola i LDL kolesterola u žena. Zaključak: Pretilost pridonosi isključivo biokemijskim parametrima u pacijenata sa shizofrenijom. U muškaraca determinira vrijednosti triglicerida, a u žena koncentracije ukupnog kolesterola i LDL kolesterola te opisuje približno 8,3 – 13,8 % varijabilnosti njihove koncentracije.

Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients with Hypercholesterolemia: A Placebo-controlled Trial

1996 ◽  
Vol 1 (3) ◽  
pp. 195-202 ◽  
Author(s):  
John M. Morgan ◽  
David M. Capuzzi ◽  
John R. Guyton ◽  
Robert M. Centor ◽  
Ronald Goldberg ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Levels

Background The present study was designed to determine the efficacy and safety of Niaspan (Kos Pharmaceuticals, Inc, Hollywood, FL), a new controlled-release formulation of niacin, in the treatment of primary hyperlipidemia, the occurrence and severity of flushing events, and potential adverse effects, particularly hepatotoxicity. Methods and Results The study was conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel comparison of Niaspan in doses of 1000 mg/day and 2000 mg/day, administered once a day at bedtime. One hundred twenty-two patients with low-density lipoprotein cholesterol levels > 4.14 mM/L (160 mg/dL) with dietary intervention and high-density lipoprotein cholesterol ≤ 1.81 mM/L (70 mg/dL) were randomized to one of three treatment groups: placebo, and 1000 mg/day or 2000 mg/day of Niaspan. Safety and efficacy measures included 12-hour serum fasting lipid and lipoprotein concentrations, serum analyte levels for major organ function, flushing diaries, and adverse event records. The placebo group demonstrated no significant changes in serum lipoprotein concentrations over the treatment period of 12 weeks, except for a slight 4% increase in high-density lipoprotein cholesterol. Niaspan significantly lowered low-density lipoprotein cholesterol levels by 6% and 14% for the 1000 mg/day and 2000 mg/day doses, respectively. High-density lipoprotein cholesterol levels rose significantly, with a 17% increase occurring at the 1000 mg/day dose and a 23% increase occurring at the 2000 mg/day dose. Niaspan (2000 mg/day) produced significant decreases of 27% and 29%, respectively, for serum lipoprotein(a) and triglyceride concentration. Although the incidence of flushing was significant, these episodes were generally well tolerated. Conclusion Niaspan administered in doses of 1000 mg/day and 2000 mg/day at bedtime were well tolerated with few side effects and produced favorable effects on the major circulating lipoproteins of patients with primary dyslipidemias as specified by the enrollment criteria.

High-density lipoprotein cholesterol and the risk of obstructive coronary artery disease beyond low-density lipoprotein cholesterol in non-diabetic individuals

2019 ◽  
Vol 27 (7) ◽  
pp. 706-714 ◽  
Author(s):  
Yong-Giun Kim ◽  
Young-Rak Cho ◽  
Gyung-Min Park ◽  
Ki-Bum Won ◽  
Soe H Ann ◽  
...  
Keyword(s):  
Coronary Artery ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Artery Disease

Aims The relationship between high-density lipoprotein cholesterol and the severity of coronary artery disease beyond low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy, remains uncertain. We evaluated the association between high-density lipoprotein cholesterol and obstructive coronary artery disease using parameters of any obstructive plaque, obstructive plaque in the left main coronary artery or proximal left anterior descending artery, and obstructive plaque in multi-vessels, according to low-density lipoprotein cholesterol levels. Methods and results We analyzed 5130 asymptomatic non-diabetics who underwent coronary computed tomography angiography for general health examination. Obstructive plaque was defined as a plaque with ≥50% luminal diameter stenosis. The participants were divided into three groups based on low-density lipoprotein cholesterol levels of ≤129, 130–159, and ≥160 mg/dl. The prevalence of any obstructive plaque (5.9% vs 6.4% vs 10.6%) and obstructive plaque in the left main coronary artery or proximal left anterior descending artery (2.1% vs 2.1% vs 4.3%) significantly increased with low-density lipoprotein cholesterol category (all p < 0.05). Compared with subjects with high-density lipoprotein cholesterol level ≥40 mg/dl, those with high-density lipoprotein cholesterol level <40 mg/dl had a significantly higher prevalence of any obstructive plaque (10.4% vs 5.1%), obstructive plaque in the left main coronary artery or proximal left anterior descending artery (3.6% vs 1.8%), and obstructive plaque in multi-vessels (4.3% vs 1.1%), only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Multiple regression analysis showed that increased high-density lipoprotein cholesterol levels were associated with a reduced risk of all obstructive coronary artery disease parameters only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Conclusion Increased high-density lipoprotein cholesterol levels were independently associated with a lower risk of obstructive coronary artery disease in asymptomatic non-diabetics with low low-density lipoprotein cholesterol levels.

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