scholarly journals Both Rare and Common Variants in PCSK9 Influence Plasma Low-Density Lipoprotein Cholesterol Level in American Indians

2015 ◽  
Vol 100 (2) ◽  
pp. E345-E349 ◽  
Author(s):  
Ching-Wei Tsai ◽  
Kari E. North ◽  
Adrienne Tin ◽  
Karin Haack ◽  
Nora Franceschini ◽  
...  
Keyword(s):  
American Indians ◽  
Genetic Architecture ◽  
Rare Variants ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Common Variants ◽  
Pcsk9 Gene ◽  
Family Based ◽  
Study Participants

Abstract Context: Elevated LDL cholesterol (LDL-C) is an important risk factor for atherosclerosis and cardiovascular disease. Variants in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been associated not only with plasma LDL-C concentration, but also with ischemic heart disease. Little is known about the genetic architecture of PCSK9 and its influence on LDL-C in American Indians. Objective: We aimed to investigate the genetic architecture in the 1p32 region encompassing PCSK9 and its influence on LDL-C in American Indians. Design: The Strong Heart Family Study (SHFS) is a family-based genetic study. Participants: Two thousand four hundred fifty eight American Indians from Arizona, Oklahoma, North Dakota, and South Dakota, who were genotyped by Illumina MetaboChip. Results: We genotyped 486 SNPs in a 3.9 Mb region at chromosome 1p32 encompassing PCSK9 in 2458 American Indians. We examined the association between these SNPs and LDL-C. For common variants (MAF ≥ 1%), meta-analysis across the three geographic regions showed common variants in PCSK9 were significantly associated with higher LDL-C. The most significant SNP rs12067569 (MAF = 1.7 %, β = 16.9 ± 3.7, P = 5.9 × 10−6) was in complete LD (r2 = 1) with a nearby missense SNP, rs505151 (E670G) (β = 15.0 ± 3.6, P = 3.6 × 10−5). For rare variants (MAF < 1%), rs11591147 (R46L, MAF = 0.9%) was associated with lower LDL-C (β = − 31.1 ± 7.1, P = 1.4 × 10−5). The mean (SD) of LDL-C was 76.9 (7.8) and 107.4 (1.0) mg/dL for those with and without the R46L mutation, respectively. One person who was homozygous for R46L had LDL-C levels of 11 mg/dL. In one family, 6 out of 8 members carrying the R46L mutation had LDL-C levels below the lower 10% percentile of LDL-C among all study participants. Conclusions: Both rare and common variants in PCSK9 influence plasma LDL-C levels in American Indians. Follow-up studies may disclose the influence of these mutations on the risk of CVD and responses to cholesterol-lowering medications.

scholarly journals A meta-analysis of Italian and Estonian individuals shows an effect of common variants in HMGCR on blood apoB levels

2019 ◽  
Vol 13 (11) ◽  
pp. 931-940
Author(s):  
Martina Rosticci ◽  
Natalia Pervjakova ◽  
Marika Kaakinen ◽  
Arrigo F Cicero ◽  
Arne P Feufer ◽  
...  
Keyword(s):  
Blood Lipids ◽  
Genetic Model ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Health Study ◽  
Common Variants ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Levels ◽  
Genome Center

Aim: The aim of the study was to explore the effects of variants at HMGCR-KIF6loci on a range of cardio-metabolic phenotypes. Methods: We analyzed the range of variants within Genetics in Brisighella Health Study and KIF6 genes using an additive genetic model on 18 cardiometabolic phenotypes in a sample of 1645 individuals from the Genetics in Brisighella Health Study and replicated in 10,662 individuals from the Estonian Genome Center University of Tartu. Results: We defined directly the effects of rs3846662:C>A at HMGCR on apoB levels. The analysis also confirmed effects of on low-density lipoprotein-cholesterol and total cholesterol levels. Variants in KIF6 gene did not reveal any associations with cardiometabolic phenotypes. Conclusion: This study highlights effect of HMGCR locus on assay-determined apoB levels, an infrequent measure of blood lipids in large studies.

scholarly journals Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2003
Author(s):  
Risa Araki ◽  
Akira Yada ◽  
Hirotsugu Ueda ◽  
Kenichi Tominaga ◽  
Hiroko Isoda
Keyword(s):  
Lipid Metabolism ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Resistance Index ◽  
Lipoprotein Cholesterol ◽  
Controlled Trials ◽  
Oh Groups ◽  
Chemical Structures ◽  
Glucose And Lipid Metabolism

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): −0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: −0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.

scholarly journals The Effect of Helicobacter pylori Eradication on Lipid Levels: A Meta-Analysis

2021 ◽  
Vol 10 (5) ◽  
pp. 904
Author(s):  
Jun Watanabe ◽  
Masato Hamasaki ◽  
Kazuhiko Kotani
Keyword(s):  
Helicobacter Pylori ◽  
Cardiovascular Diseases ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Levels ◽  
Pubmed Database ◽  
H Pylori ◽  
Meta Analyses

Introduction: Helicobacter pylori (H. pylori) infection is positively associated with cardiovascular diseases, but the involvement of lipids in this association remains unclear. The present study reviewed the changes in circulating lipid levels following H. pylori eradication. Methods: A PubMed database was searched until December 2020 to identify randomized control trials (RCTs) and non-RCTs investigating the effect of H. pylori eradication on the lipid levels in inverse variance-weighted, random-effects meta-analyses. Results: A total of 24 studies (four RCTs and 20 non-RCTs) with 5270 participants were identified. The post-eradication levels were increased for high-density lipoprotein cholesterol (HDL-C; mean difference (MD) 2.28 mg/dL, 95% confidence interval (CI) 1.90 to 2.66) and triglyceride (TG; MD 3.22 mg/dL, 95% CI 1.13 to 5.31) compared with the pre-eradication levels. H. pylori eradication resulted in little to no difference in the low-density lipoprotein-cholesterol levels (MD −2.33 mg/dL, 95% CI −4.92 to 0.26). In the analyses of RCTs only, the findings for elevated HDL-C levels, but not TG, were robust. Conclusions: H. pylori eradication increases the HDL-C levels. Further studies are needed to elucidate the effects of lipid changes following H. pylori eradication on cardiovascular diseases.

scholarly journals The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis

Spinal Cord ◽  
2021 ◽  
Author(s):  
Peter Francis Raguindin ◽  
Gion Fränkl ◽  
Oche Adam Itodo ◽  
Alessandro Bertolo ◽  
Ramona Maria Zeh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Blood Pressure ◽  
Spinal Cord ◽  
Cardiovascular Risk ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Cord Injury

Abstract Study design Systematic review and meta-analysis. Objective To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). Methods We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). Results We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, −14.5 mmHg, 95% CI −19.2, −9.9; −7.0 mmHg 95% CI −9.2, −4.8, respectively), lower triglycerides (−10.9 mg/dL, 95% CI −19.7, −2.1), total cholesterol (−9.9 mg/dL, 95% CI −14.5, −5.4), high-density lipoprotein (−1.7 mg/dL, 95% CI −3.3, −0.2) and low-density lipoprotein (−5.8 mg/dL, 95% CI −9.0, −2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (−10.3 mmHg, 95% CI −13.4, −7.1; −5.3 mmHg 95% CI −7.5, −3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. Conclusion In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.

scholarly journals Sulforaphane ameliorates lipid profile in rodents: an updated systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaili Du ◽  
Yuxin Fan ◽  
Dan Li
Keyword(s):  
Systematic Review ◽  
Weight Control ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Disease Model ◽  
Density Lipoprotein ◽  
Liver Weight ◽  
Lipoprotein Cholesterol ◽  
Alcoholic Fatty Liver

AbstractSulforaphane (SFN), a naturally-occurring isothiocyanate enriched in cabbage and broccoli, has been provided as food supplements to improve weight management and reduce lipid levels. However, its effects on serum lipid profiles are contradictory. In this review, a meta-analysis and systematic review of SFN on lipid reduction and weight control is assessed with mice and rats fed on high-fat diet. The effects of SFN supplementation were evaluated by weighted mean difference (WMD) in body weight (BW), liver weight (LW) and also by its effect on serum lipids. A random-effects model was applied to estimate the overall summary effect. SFN reduced BW (WMD: − 2.76 g, 95% CI: − 4.19, − 1.34) and LW (WMD: − 0.93 g, 95% CI: − 1.63, − 0.23) significantly in our ten trials. Its effects on serum total cholesterol (TC) (WMD: − 15.62 mg/dL, 95% CI: − 24.07, − 7.18), low-density lipoprotein cholesterol (LDL-C) (WMD: − 8.35 mg/dL, 95% CI: − 15.47, − 1.24) and triglyceride (TG) (WMD: − 40.85 mg/dL, 95% CI: − 67.46, − 14.24) were significant except for high-density lipoprotein cholesterol (HDL-C) component (WMD: 1.05 mg/dL, 95% CI: − 3.44, 5.54). However, species, disease model, duration, SFN dosage as well as route of administration did not explain the heterogeneity among studies. In summary, these findings provide new insights concerning preclinical strategies for treating diseases including obesity, diabetes, hypertension, non-alcoholic fatty liver disease as well as cardiovascular disease with SFN supplements.

scholarly journals The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Alexey Meshkov ◽  
Alexandra Ershova ◽  
Anna Kiseleva ◽  
Evgenia Zotova ◽  
Evgeniia Sotnikova ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Significant Proportion ◽  
Density Lipoprotein ◽  
Genetic Diagnostics ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gene Variants ◽  
Systematic Analysis ◽  
Pcsk9 Gene ◽  
Cholesterol Levels

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

scholarly journals Potential Biomarkers for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 23 (2) ◽  
pp. 602
Author(s):  
Ka Young Kim ◽  
Ki Young Shin ◽  
Keun-A Chang
Keyword(s):  
Systematic Review ◽  
Uric Acid ◽  
Cognitive Impairment ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Cochrane Library ◽  
Blood Proteins ◽  
Post Stroke

Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.

scholarly journals Maternal lipid profile and risk of pre-eclampsia in African pregnant women: A systematic review and meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243538
Author(s):  
Endalamaw Tesfa ◽  
Endalkachew Nibret ◽  
Abaineh Munshea
Keyword(s):  
Pregnant Women ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Profiles ◽  
Maternal Serum ◽  
Lipoprotein Cholesterol ◽  
Low Density Lipoprotein Cholesterol ◽  
Standardized Mean Difference

Introduction Some studies have reported the association between maternal serum lipid profile abnormalities and pre-eclampsia. However, many studies have reported controversial results. Hence, this systematic review and meta-analysis was planned to generate summarized evidence on the association between maternal serum lipid profiles and pre-eclampsia in African women. Methods Four electronic databases such as; PubMed, Hinari, Google Scholar, and African Journals Online were searched for studies published in English. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument and Newcastle-Ottawa Scale were used for data extraction and quality assessment of the included studies. The meta- regression analysis was performed by Stata 14 software. The standardized mean difference (SMD) values of lipid profiles were computed to assess their association with pre-eclampsia at 95% CI. Results In this review a total of 15 observational studies were included. The mean values of triglyceride (TG), total cholesterol (TC), low density lipoprotein- cholesterol (LDL-c) and very low density lipoprotein- cholesterol (VLDL-c) were significantly higher in pre-eclamptic women as compared with normotensive pregnant women (TG = 229.61±88.27 and 147.00 ± 40.47, TC = 221.46 ± 45.90 and 189.67 ± 39.18, LDL = 133.92 ± 38.77 and 112.41 ± 36.08, VLDL = 41.44 ± 19.68 and 26.64 ± 7.87), respectively. The serum high density lipoprotein cholesterol (HDL-c) level was lower, but it is not statistically significant (HDL-c = 51.02 ± 16.01 and 61.80 ± 25.63) in pre-eclamptic women as compared with controls. The pooled standardized mean difference (SMD) of TG, TC, LDL-C and VLDL-C were significantly increased in pre-eclamptic women as compared with normotensive pregnant women with the SMD of (TG = 1.65 (1.10, 2.21), TC = 0.84 (0.40, 1.29), LDL-C = 0.95 (0.46, 1.45) and VLDL-C = 1.27 (0.72, 1.81)) at 95% CI, respectively, but the pooled SMD of HDL-cholesterol was decreased in pre-eclamptic women as compared with normotensive pregnant women (SMD = -0.91 (95% CI: -1.43, -0.39). Conclusions In this review, the maternal serum levels of TG, TC, LDL-c and VLDL-c were significantly associated with the risk of preeclampsia. However, HDL- cholesterol was not significantly associated but it was lower in pre-eclamptic women. Further, large scale prospective studies should verify these outcomes and it is recommended that lipid profiles should be included as a routine diagnostic test for pre-eclamptic women.

scholarly journals Common Variants of Homocysteine Metabolism Pathway Genes and Risk of Type 2 Diabetes and Related Traits in Indians

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ganesh Chauhan ◽  
Ismeet Kaur ◽  
Rubina Tabassum ◽  
Om Prakash Dwivedi ◽  
Saurabh Ghosh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Cardiovascular Disorder ◽  
Common Variants ◽  
Study Population ◽  
North Indians ◽  
Sample Set

Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variantMTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR=0.78(95%  CI=0.67–0.92),P=0.003) and was also associated with 2 h postload plasma glucose (P=0.04), high-density lipoprotein cholesterol (P=0.004), and total cholesterol (P=0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.

Abstract 367: Extreme High-Density Lipoprotein Cholesterol Genetics: An Assortment of Large and Small Polygenic Effects

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jacqueline S Dron ◽  
Jian Wang ◽  
Cécile Low-Kam ◽  
Sumeet A Khetarpal ◽  
John F Robinson ◽  
...  
Keyword(s):  
Large Scale ◽  
Genetic Basis ◽  
Rare Variants ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Copy Number Variations ◽  
Genome Wide Association Studies ◽  
Common Variants ◽  
Targeted Next Generation Sequencing ◽  
Common Genetic Variants

Rationale: Although HDL-C levels are known to have a complex genetic basis, most studies have focused solely on identifying rare variants with large phenotypic effects to explain extreme HDL-C phenotypes. Objective: Here we concurrently evaluate the contribution of both rare and common genetic variants, as well as large-scale copy number variations (CNVs), towards extreme HDL-C concentrations. Methods: In clinically ascertained patients with low ( N =136) and high ( N =119) HDL-C profiles, we applied our targeted next-generation sequencing panel (LipidSeq TM ) to sequence genes involved in HDL metabolism, which were subsequently screened for rare variants and CNVs. We also developed a novel polygenic trait score (PTS) to assess patients’ genetic accumulations of common variants that have been shown by genome-wide association studies to associate primarily with HDL-C levels. Two additional cohorts of patients with extremely low and high HDL-C (total N =1,746 and N =1,139, respectively) were used for PTS validation. Results: In the discovery cohort, 32.4% of low HDL-C patients carried rare variants or CNVs in primary ( ABCA1 , APOA1 , LCAT ) and secondary ( LPL , LMF1 , GPD1 , APOE ) HDL-C–altering genes. Additionally, 13.4% of high HDL-C patients carried rare variants or CNVs in primary ( SCARB1 , CETP , LIPC , LIPG ) and secondary ( APOC3 , ANGPTL4 ) HDL-C–altering genes. For polygenic effects, patients with abnormal HDL-C profiles but without rare variants or CNVs were ~2-fold more likely to have an extreme PTS compared to normolipidemic individuals, indicating an increased frequency of common HDL-C–associated variants in these patients. Similar results in the two validation cohorts demonstrate that this novel PTS successfully quantifies common variant accumulation, further characterizing the polygenic basis for extreme HDL-C phenotypes. Conclusions: Patients with extreme HDL-C levels have various combinations of rare variants, common variants, or CNVs driving their phenotypes. Fully characterizing the genetic basis of HDL-C levels must extend to encompass multiple types of genetic determinants—not just rare variants—to further our understanding of this complex, controversial quantitative trait.

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