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Annabelle Rodriguez - One of the best experts on this subject based on the ideXlab platform.
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abstract 413 lipoprotein SCARB1 intronic variant associated with increased coronary heart disease risk affects cardio protective gene networks
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Diana Golden, Sameet Mehta, Antonina Kolmakova, Annabelle RodriguezAbstract:Introduction: We previously reported a common intronic SCARB1 (12q24.31) variant, rs10846744, located in an enhancer region, to be significantly associated with coronary artery disease (CAD) in the Multi-Ethnic Study of Atherosclerosis (MESA). RNA-Seq showed expression of the immune checkpoint inhibitor lymphocyte activation gene 3 ( LAG3 , 12p13.31), to be 5-fold lower in carriers of the risk allele, while low plasma LAG3 protein levels were also significantly associated with increased CAD risk in MESA, after multivariate regression analysis. Hypothesis: That the SCARB1 rs10846744 variant disrupts long-range transcriptional regulation of LAG3 disturbing cardio-protective and anti-inflammatory gene networks to promote CAD. Methods and Results: Using functional genomics (HiC global chromatin capture, ChIP-Seq and RNA-Seq) in reference and risk EBV-transformed B lymphocytes to assess 3D chromatin architecture and gene-gene interactions at a 2.5kb resolution, we did not observe direct chromatin contacts between SCARB1 and LAG3. In the reference allele, an enhancer-rich intermediate contact (12q13.13) was found containing genes associated with cholesterol ( SOAT2 ) and NR2F2 signaling ( RARG ). This same 12q13.13 region was in direct contact with 22q12.3 ( APOLI) , an apoprotein associated with HDL and innate immunity. Micro-looping within the rs10846744 12q24.31 region showed direct contacts with other enhancers ( NCOR2 ) and cardiovascular loci ( TMEM132B ), while LAG3 micro-looping on 12p13.31 was associated with immune regulatory networks ( CD4 ). Loci associated with viral infection, cytokine production, heart failure and autoimmunity were also identified. NR2F2 disrupted contacts in the risk allele, implicating NR2F2 as a dysfunctional rs10846744 transcriptional repressor altering gene networks. The risk allele included contacts near PCSK9 , VLDLR and 2q33.1, a CAD locus. Conclusion: Functional genomics of the SCARB1 rs10846744 enhancer region identified a number of intra- and inter-chromosomal chromatin contacts in reference cells that were markedly disrupted in risk cells. Perturbing NR2F2 and/or genes disrupted in the SCARB1 -NR2F2 immuno-cardiovascular axis may protect against CAD in the rs10846744 risk population.
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association of the lipoprotein receptor SCARB1 common missense variant rs4238001 with incident coronary heart disease
PLOS ONE, 2015Co-Authors: Ani Manichaikul, Xin-qun Wang, Wendy S. Post, David M Herrington, Stephen S Rich, Solomon K Musani, James G Wilson, Annabelle RodriguezAbstract:Background Previous studies in mice and humans have implicated the lipoprotein receptor SCARB1 in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of SCARB1 missense single nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease (CHD). Methods and Results Genotypes for rs4238001 were imputed for 2,319 White, 1,570 African American, and 1,292 Hispanic-American MESA participants using the 1,000 Genomes reference set. Cox proportional hazards models were used to determine association of rs4238001 with incident CHD, with adjustments for age, sex, study site, principal components of ancestry, body mass index, diabetes status, serum creatinine, lipid levels, hypertension status, education and smoking exposure. Meta-analysis across race/ethnic groups within MESA showed statistically significant association of the T allele with higher risk of CHD under a consistent and formally adjudicated definition of CHD events in this contemporary cohort study (hazard ratio [HR]=1.49, 95% CI [1.04, 2.14], P = 0.028). Analyses combining MESA with additional population-based cohorts expanded our samples in Whites (total n = 11,957 with 871 CHD events) and African Americans (total n = 5,962 with 355 CHD events) and confirmed an increased risk of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], P = 0.013), in African Americans (HR of 1.49 with 95% CI [1.07, 2.06], P = 0.019), in males (HR of 1.29 with 95% CI [1.08, 1.54], P = 4.91x10-3) and in White males (HR of 1.24 with 95% CI [1.03, 1.51], P = 0.026). Conclusion SCARB1 missense rs4238001 is statistically significantly associated with incident CHD across a large population of multiple race/ethnic groups.
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abstract 18570 intronic SCARB1 scavenger receptor class b type i sr bi rs10846744 variant mediates functional effect by enhancer activity
Circulation, 2013Co-Authors: Rashid Ali, Antonina Kolmakova, Lane K Christenson, Annabelle RodriguezAbstract:Objective: We previously reported the significant association of SCARB1 intronic rs10846744 in reducing odds ratio for incident coronary heart disease (CHD) in participants of the Multi-Ethnic Study of Atherosclerosis. Using in vitro and ex vivo approaches, we sought to define the underlining molecular mechanism for this clinical association. Methods and results: Using publicly available genome databases, a bioinformatic screen revealed that rs10846744 resided in a region exhibiting DNase I hypersensitivity and H3K4me1 chromatin methylation markers. Gel shift assays revealed significantly lower binding of nuclear proteins to the probe expressing the risk C allele for CHD ( p p p =0.0136, q =0.2437) and lower levels of lysolipids (46% lower, p =0.0043, q =0.1605). Conclusion: The intronic rs10846744 variant resides within a functionally active regulatory region of SCARB1 , without directly regulating SR-BI expression itself. Our results confirm the importance of dissecting the pathway by which this region influences CHD.
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association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease the multi ethnic study of atherosclerosis
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Ani Manichaikul, Wendy S. Post, Adam C Naj, David M Herrington, Stephen S Rich, Annabelle RodriguezAbstract:Objective—We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in ea...
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a synonymous variant in scavenger receptor class b type i gene is associated with lower sr bi protein expression and function
Atherosclerosis, 2010Co-Authors: Jason Constantineau, Michael West, Lane K Christenson, Erin Greason, Megan E Filbin, Jeffrey S Kieft, Martha Z Carletti, Annabelle RodriguezAbstract:Objective A synonymous variant within scavenger receptor class B type I gene (SCARB1), exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans. The objective was to determine if rs5888 decreased SR-BI protein expression and function in vitro.
Samuel F Berkovic - One of the best experts on this subject based on the ideXlab platform.
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clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by scarb2 mutations
Epilepsia, 2011Co-Authors: Guido Rubboli, Leanne M Dibbens, Samuel F Berkovic, Silvana Franceschetti, Laura Canafoglia, Antonio Gambardella, P Riguzzi, Claudio Campieri, Adriana Magaudda, C A TassinariAbstract:Summary Purpose: Mutations of the SCARB2 gene cause action myoclonus renal failure syndrome (AMRF), a rare condition that combines progressive myoclonus epilepsy (PME) with severe renal dysfunction. We describe the clinical and neurophysiologic features of PME associated with SCARB2 mutations without renal impairment. Methods: Clinical and neurophysiologic investigations, including wakefulness and sleep electroencephalography (EEG), polygraphic recording (with jerk-locked back-averaging and analysis of the EEG–EMG (electromyography) relationship by coherence spectra and phase calculation), multimodal evoked potentials, and electromyography were performed on five Italian patients with SCARB2 mutations. Key Findings: The main clinical features were adolescent–young adulthood onset, progressive action myoclonus, ataxia, absence of cognitive deterioration and, in most cases, epilepsy. The severity of the epilepsy could vary from uncontrolled seizures and status epilepticus in patients with adolescent onset to absent or rare seizures in patients with adult onset. Relevant neurophysiologic findings were a pronounced photosensitivity and massive action myoclonus associated with rhythmic myoclonic jerks at a frequency of 12–20 Hz, clinically resembling a postural tremor. The cortical origin of rhythmic myoclonus was demonstrated mainly by coherence and phase analysis of EEG–EMG signals indicating a significant EEG–EMG coupling and a direct corticospinal transfer. Significance: Our patients with SCARB2 mutations showed the clinical and neurophysiologic phenotype of PME, in which epilepsy could be extremely severe, extending the spectrum reported in the typical AMRF syndrome. Patients with PME of unknown origin of adolescent or young adult onset, with these neurophysiologic features, should be tested for SCARB2 mutations, even in the absence of renal impairment.
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mutation of scarb2 in a patient with progressive myoclonus epilepsy and demyelinating peripheral neuropathy
JAMA Neurology, 2011Co-Authors: Leanne M Dibbens, Ioannis Karakis, Marta A Bayly, Daniel J Costello, Andrew J Cole, Samuel F BerkovicAbstract:Objective To report the detection of mutations in the SCARB2 gene in a previously described patient with progressive myoclonus epilepsy (PME) and demyelinating peripheral neuropathy. Design Case report. Setting Epilepsy Genetics Research Laboratory and Epilepsy Service in a tertiary care center. Patient A 27-year old male patient with PME with preserved intellect and peripheral neuropathy. Results We have solved a previously reported case of PME, preserved intellect, and demyelinating peripheral neuropathy. The patient is a compound heterozygote for 2 mutations in the SCARB2 gene, which has recently been found to be a cause of PME. Conclusions Demyelinating neuropathy is a clinical clue to the presence of SCARB2 mutations in PME.
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array based gene discovery with three unrelated subjects shows scarb2 limp 2 deficiency causes myoclonus epilepsy and glomerulosclerosis
American Journal of Human Genetics, 2008Co-Authors: Leanne M Dibbens, Samuel F Berkovic, Alicia Oshlack, Jeremy D Silver, Marina Katerelos, Danya F VearsAbstract:Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies.
Gudmundur I Eyjolfsson - One of the best experts on this subject based on the ideXlab platform.
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rare SCARB1 mutations associate with high density lipoprotein cholesterol but not with coronary artery disease
European Heart Journal, 2018Co-Authors: Anna Helgadottir, Patrick Sulem, Gudmundur Thorgeirsson, Isleifur Olafsson, Solveig Gretarsdottir, Gudmar Thorleifsson, Brynjar O Jensson, Gudny A Arnadottir, Gudmundur I EyjolfssonAbstract:Aims Scavenger receptor Class B Type 1 (SR-BI) is a major receptor for high-density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment might be an independent marker of cardiovascular risk. We tested the hypothesis that alleles in or close to SCARB1 that associate with elevated levels of HDL-C also associate with increased risk of CAD in the relatively homogeneous population of Iceland. Methods and results Using a large resource of whole-genome sequenced Icelanders, we identified thirteen SCARB1 coding mutations that we examined for association with HDL-C (n = 136 672). Three rare SCARB1 mutations, encoding p.G319V, p.V111M, and p.V32M (combined allelic frequency = 0.2%) associate with elevated levels of HDL-C (p.G319V: β = 11.1 mg/dL, P = 8.0 × 10-7; p.V111M: β = 8.3 mg/dL, P = 1.1 × 10-6; p.V32M: β = 10.2 mg/dL, P = 8.1 × 10-4). These mutations do not associate with CAD (36 886 cases/306 268 controls) (odds ratio = 0.90, 95% confidence interval 0.67-1.22, P = 0.49), despite effects on HDL-C comparable to that reported for p.P376L, both in terms of direction and magnitude. Furthermore, HDL-C raising alleles of three common SCARB1 non-coding variants, including one previously unreported (rs61941676-C: β = 1.25 mg/dL, P = 1.7 × 10-18), and of one low frequency coding variant (p.V135I) that independently associate with higher HDL-C, do not confer increased risk of CAD. Conclusion Elevated HDL-C due to genetically compromised SR-BI function is not a marker of CAD risk.
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abstract 19040 different SCARB1 locus variants associate with hdl cholesterol and the risk of coronary artery disease
Circulation, 2016Co-Authors: Anna Helgadottir, Patrick Sulem, Gudmundur Thorgeirsson, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari StefanssonAbstract:Background and objective: Scavenger receptor class B type 1 (SR-B1), encoded by the SCARB1 gene, promotes uptake of cholesterol from circulating HDL and plays a role in reverse cholesterol transport. Genome-wide association studies (GWAS) have identified common variants at the SCARB1 locus that associate with HDL-C and rare SCARB1 coding variants have been shown to increase HDL-C. Recently a rare missense variant p.P376L in SCARB1 that raises HDL-C was reported to increase CAD risk, in contrast to expected cardiovascular protection as observed in epidemiologic studies. GWAS studies have also found common SCARB1 locus variants that associate with levels of vitamin E and Lp-PLA2 activity, highlighting the complexity of the association signals at this locus. We aim to examine the relationship between HDL-C associating variants at the SCARB1 locus and the risk of CAD. Methods and results: We examined all sequence variants in the SCARB1 locus identified through whole-genome sequencing of 8,453 Icelanders and subsequently imputed into a large population-based dataset for association with HDL-C (n= 136,672) and CAD (39,904 cases/306,338 controls). Apart from replicating association of two common HDL-C variants we identified the third common variant that independently associates with HDL-C (β= -1.25 mg/dL, P =1.7x10 -18 ). In addition, we identified two rare missense variants, occurring in the large extracellular loop of the SR-BI protein, that associate with elevated levels of HDL-C (p.G319V: β=11.12 mg/dL, P =8.0x10 -7 and p.V111M: β=8.25 mg/dL, P =1.1x10 -6 ). None of the five independent variants that associate with HDL-C at the SCARB1 locus associate with CAD. However, another intronic SCARB1 variant, that correlated with markers previously shown to associate with Lp-PLA2 and vitamin E, associates with CAD (OR=1.08, P =1.9x10 -8 ), but not with HDL-C. Conclusion: While rare and common HDL-C associating variants at the SCARB1 locus do not associate with CAD, a different common variant at the same locus does. This suggests that the CAD associating locus variant mediates its effect through HDL-C independent mechanisms.
Gudmundur Thorgeirsson - One of the best experts on this subject based on the ideXlab platform.
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rare SCARB1 mutations associate with high density lipoprotein cholesterol but not with coronary artery disease
European Heart Journal, 2018Co-Authors: Anna Helgadottir, Patrick Sulem, Gudmundur Thorgeirsson, Isleifur Olafsson, Solveig Gretarsdottir, Gudmar Thorleifsson, Brynjar O Jensson, Gudny A Arnadottir, Gudmundur I EyjolfssonAbstract:Aims Scavenger receptor Class B Type 1 (SR-BI) is a major receptor for high-density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment might be an independent marker of cardiovascular risk. We tested the hypothesis that alleles in or close to SCARB1 that associate with elevated levels of HDL-C also associate with increased risk of CAD in the relatively homogeneous population of Iceland. Methods and results Using a large resource of whole-genome sequenced Icelanders, we identified thirteen SCARB1 coding mutations that we examined for association with HDL-C (n = 136 672). Three rare SCARB1 mutations, encoding p.G319V, p.V111M, and p.V32M (combined allelic frequency = 0.2%) associate with elevated levels of HDL-C (p.G319V: β = 11.1 mg/dL, P = 8.0 × 10-7; p.V111M: β = 8.3 mg/dL, P = 1.1 × 10-6; p.V32M: β = 10.2 mg/dL, P = 8.1 × 10-4). These mutations do not associate with CAD (36 886 cases/306 268 controls) (odds ratio = 0.90, 95% confidence interval 0.67-1.22, P = 0.49), despite effects on HDL-C comparable to that reported for p.P376L, both in terms of direction and magnitude. Furthermore, HDL-C raising alleles of three common SCARB1 non-coding variants, including one previously unreported (rs61941676-C: β = 1.25 mg/dL, P = 1.7 × 10-18), and of one low frequency coding variant (p.V135I) that independently associate with higher HDL-C, do not confer increased risk of CAD. Conclusion Elevated HDL-C due to genetically compromised SR-BI function is not a marker of CAD risk.
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abstract 19040 different SCARB1 locus variants associate with hdl cholesterol and the risk of coronary artery disease
Circulation, 2016Co-Authors: Anna Helgadottir, Patrick Sulem, Gudmundur Thorgeirsson, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari StefanssonAbstract:Background and objective: Scavenger receptor class B type 1 (SR-B1), encoded by the SCARB1 gene, promotes uptake of cholesterol from circulating HDL and plays a role in reverse cholesterol transport. Genome-wide association studies (GWAS) have identified common variants at the SCARB1 locus that associate with HDL-C and rare SCARB1 coding variants have been shown to increase HDL-C. Recently a rare missense variant p.P376L in SCARB1 that raises HDL-C was reported to increase CAD risk, in contrast to expected cardiovascular protection as observed in epidemiologic studies. GWAS studies have also found common SCARB1 locus variants that associate with levels of vitamin E and Lp-PLA2 activity, highlighting the complexity of the association signals at this locus. We aim to examine the relationship between HDL-C associating variants at the SCARB1 locus and the risk of CAD. Methods and results: We examined all sequence variants in the SCARB1 locus identified through whole-genome sequencing of 8,453 Icelanders and subsequently imputed into a large population-based dataset for association with HDL-C (n= 136,672) and CAD (39,904 cases/306,338 controls). Apart from replicating association of two common HDL-C variants we identified the third common variant that independently associates with HDL-C (β= -1.25 mg/dL, P =1.7x10 -18 ). In addition, we identified two rare missense variants, occurring in the large extracellular loop of the SR-BI protein, that associate with elevated levels of HDL-C (p.G319V: β=11.12 mg/dL, P =8.0x10 -7 and p.V111M: β=8.25 mg/dL, P =1.1x10 -6 ). None of the five independent variants that associate with HDL-C at the SCARB1 locus associate with CAD. However, another intronic SCARB1 variant, that correlated with markers previously shown to associate with Lp-PLA2 and vitamin E, associates with CAD (OR=1.08, P =1.9x10 -8 ), but not with HDL-C. Conclusion: While rare and common HDL-C associating variants at the SCARB1 locus do not associate with CAD, a different common variant at the same locus does. This suggests that the CAD associating locus variant mediates its effect through HDL-C independent mechanisms.
Wendy S. Post - One of the best experts on this subject based on the ideXlab platform.
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Lp-PLA2, scavenger receptor class B type i gene (SCARB1) rs10846744 variant, and cardiovascular disease
PloS one, 2018Co-Authors: Ani Manichaikul, Dawn M. Waterworth, Xin-qun Wang, Jeanette Erdmann, Guillaume Lettre, Joshua C. Bis, Mary Cushman, Nancy S. Jenny, Wendy S. PostAbstract:Background We previously reported association of SCARB1 SNP rs10846744 with common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since rs10846744 has been reported in association with Lp-PLA2 mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis. Methods We first examined association of rs10846744 in CVD in multiple large-scale consortium-based genome-wide association studies. We further examined 27 parameters of interest, including Lp-PLA2 mass and activity, inflammatory markers, and plasma phospholipid fatty acids, and fatty acid ratios in participants from the Multi-Ethnic Study of Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744 with cIMT and incident CVD. Finally, we examined the association of rs10846744 with Lp-PLA2 activity, cardiovascular outcomes, and interaction with the Lp-PLA2 inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies. Results SCARB1 rs10846744 was associated with coronary artery disease events in CARDIoGRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P = 1.4x10-4). In combined analysis across race/ethnic groups in MESA, rs10846744 was associated with Lp-PLA2 mass (P = 0.04) and activity (P = 0.001), homocysteine (P = 0.03), LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01), docosapentaenoic acid [DPA] (P = 0.04), DPA/ eicosapentaenoic acid [EPA] ratio (P = 0.002), and DHA/EPA ratio (P = 0.008). Lp-PLA2 activity was identified as a mediator of rs10846744 with cIMT in a basic model (P = 8x10-5), but not after adjustment for CVD risk factors. There was no interaction or modifier effect of the Lp-PLA2 inhibitor darapladib assignment on the relationship between rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. Summary SCARB1 rs10846744 is significantly associated with Lp-PLA2 activity, atherosclerosis, and CVD events, but Lp-PLA2 activity is not a mediator in the association of rs10846744 with cIMT in MESA.
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association of the lipoprotein receptor SCARB1 common missense variant rs4238001 with incident coronary heart disease
PLOS ONE, 2015Co-Authors: Ani Manichaikul, Xin-qun Wang, Wendy S. Post, David M Herrington, Stephen S Rich, Solomon K Musani, James G Wilson, Annabelle RodriguezAbstract:Background Previous studies in mice and humans have implicated the lipoprotein receptor SCARB1 in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of SCARB1 missense single nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease (CHD). Methods and Results Genotypes for rs4238001 were imputed for 2,319 White, 1,570 African American, and 1,292 Hispanic-American MESA participants using the 1,000 Genomes reference set. Cox proportional hazards models were used to determine association of rs4238001 with incident CHD, with adjustments for age, sex, study site, principal components of ancestry, body mass index, diabetes status, serum creatinine, lipid levels, hypertension status, education and smoking exposure. Meta-analysis across race/ethnic groups within MESA showed statistically significant association of the T allele with higher risk of CHD under a consistent and formally adjudicated definition of CHD events in this contemporary cohort study (hazard ratio [HR]=1.49, 95% CI [1.04, 2.14], P = 0.028). Analyses combining MESA with additional population-based cohorts expanded our samples in Whites (total n = 11,957 with 871 CHD events) and African Americans (total n = 5,962 with 355 CHD events) and confirmed an increased risk of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], P = 0.013), in African Americans (HR of 1.49 with 95% CI [1.07, 2.06], P = 0.019), in males (HR of 1.29 with 95% CI [1.08, 1.54], P = 4.91x10-3) and in White males (HR of 1.24 with 95% CI [1.03, 1.51], P = 0.026). Conclusion SCARB1 missense rs4238001 is statistically significantly associated with incident CHD across a large population of multiple race/ethnic groups.
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association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease the multi ethnic study of atherosclerosis
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Ani Manichaikul, Wendy S. Post, Adam C Naj, David M Herrington, Stephen S Rich, Annabelle RodriguezAbstract:Objective—We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in ea...
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association of scavenger receptor class b type i polymorphisms with subclinical atherosclerosis the multi ethnic study of atherosclerosis
Circulation-cardiovascular Genetics, 2010Co-Authors: Adam C Naj, Wendy S. Post, David M Herrington, Stephen S Rich, Michael West, W Linda H Kao, Bruce A Wasserman, Annabelle RodriguezAbstract:Background— Little is known about the association of scavenger receptor class B type I ( SCARB1 ) single-nucleotide polymorphisms (SNPs) and subclinical atherosclerosis, particularly in subjects of different racial/ethnic backgrounds. We examined this relationship in the Multi-Ethnic Study of Atherosclerosis. Methods and Results— Forty-three SCARB1 -tagging SNPs were genotyped. Baseline examinations included fasting lipids and subclinical atherosclerosis phenotypes (coronary artery calcification, common carotid intimal-medial artery thickness [CCIMT], and internal carotid intimal-medial artery thickness). Examining SNP associations with different subclinical atherosclerosis phenotypes across multiple racial/ethnic groups with adjustment for multiple covariates, we found that the C allele of SNP rs10846744 was associated with higher CCIMT in African American ( P =0.03), Chinese ( P =0.02), European American ( P =0.05), and Hispanic participants ( P =0.03) and was strongly associated in pooled analyses ( P =0.0002). The results also showed that the association of this SNP with CCIMT was independent of lipids and other well-established cardiovascular risk factors. Stratifying by sex, there seemed to be a strong association of rs10846744 with CCIMT in women, but no genotype-sex interactions were observed. Conclusions— Variation in SCARB1 at rs10846744 was significantly associated with CCIMT across racial/ethnic groups in Multi-Ethnic Study of Atherosclerosis. Received August 19, 2009; accepted November 17, 2009. # CLINICAL PERSPECTIVE {#article-title-2}
