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See detailThe Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis
Hipp Epouse D'amico, Géraldine UL; Vaillant, Michel; Diederich, Nico J. et al

in Frontiers in Aging Neuroscience (2018), 10

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies ... [more ▼]

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches. [less ▲]

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See detailPancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity
Staaf, Johan; Labmayr, Viktor; Paulmichl, Katharina et al

in Pancreas (2017)

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See detailRebound hyperglycaemia in diabetic cats
Roomp, Kirsten UL; Rand, Jacquie

in Journal of Feline Medicine and Surgery (2015)

Objectives Rebound hyperglycaemia (also termed Somogyi effect) is defined as hyperglycaemia caused by the release of counter-regulatory hormones in response to insulin induced hypoglycaemia, and is widely ... [more ▼]

Objectives Rebound hyperglycaemia (also termed Somogyi effect) is defined as hyperglycaemia caused by the release of counter-regulatory hormones in response to insulin induced hypoglycaemia, and is widely believed to be common in diabetic cats. However, studies in human diabetic patients over the last quarter century have rejected the common occurrence of this phenomenon. Therefore, we evaluated the occurrence and prevalence of rebound hyperglycaemia in diabetic cats. Methods In a retrospective study, 10,767 blood glucose curves of 55 cats treated with glargine using an intensive blood glucose regulation protocol with a median of five blood glucose measurements per day were evaluated for evidence of rebound hyperglycaemic events, defined in two different ways (with and without an insulin resistance component). Results While biochemical hypoglycaemia occurred frequently, blood glucose curves consistent with rebound hyperglycaemia with insulin resistance was confined to four single events in four different cats. In 14/55 of cats (25%), a median of 1.5% (range 0.32–7.7%) of blood glucose curves were consistent with rebound hyperglycaemia without an insulin resistance component; this represented 0.42% of blood glucose curves in both affected and unaffected cats. Conclusions and relevance We conclude that despite the frequent occurrence of biochemical hypoglycaemia, rebound hyperglycaemia is rare in cats treated with glargine on a protocol aimed at tight glycaemic control. For glargine-treated cats, insulin dose should not be reduced when there is hyperglycaemia in the absence of biochemical or clinical evidence of hypoglycaemia. [less ▲]

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See detailEvaluation of detemir in diabetic cats managed with a protocol for intensive blood glucose control
Roomp, Kirsten UL; Rand, Jacquie

in Journal of Feline Medicine and Surgery (2012), 14(8), 566-572

The aim of this study was to report outcomes using detemir and a protocol aimed at intensive blood glucose control with home monitoring in diabetic cats, and to compare the results with a previous study ... [more ▼]

The aim of this study was to report outcomes using detemir and a protocol aimed at intensive blood glucose control with home monitoring in diabetic cats, and to compare the results with a previous study using the same protocol with glargine. Eighteen cats diagnosed with diabetes and previously treated with other insulins were included in the study. Data was provided by owners who joined the online German Diabetes-Katzen Forum. The overall remission rate was 67%. For cats that began the protocol before or after 6 months of diagnosis, remission rates were 81% and 42%, respectively (P = 0.14). No significant differences were identified between the outcomes for the glargine and detemir studies, with the exception of three possibly interrelated factors: a slightly older median age of the detemir cohort at diabetes diagnosis, a higher rate of chronic renal disease in the detemir cohort and lower maximal dose for insulin detemir. [less ▲]

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See detailPredicting interactions between T cell receptors and MHC-peptide complexes
Roomp, Kirsten UL; Domingues, Francisco S.

in Molecular Immunology (2011), 48(4), 553-562

Conserved interactions between T cell receptors (TCRs) and major histocompatibility complex (MHC) proteins with bound peptide antigens are not well understood. In order to gain a better understanding of ... [more ▼]

Conserved interactions between T cell receptors (TCRs) and major histocompatibility complex (MHC) proteins with bound peptide antigens are not well understood. In order to gain a better understanding of the interaction modes of human TCR variable (V) regions, we have performed a structural analysis of the TCRs bound to their MHC-peptide ligands in human, using the available structural models determined by X-ray crystallography. We identified important differences to previous studies in which such interactions were evaluated. Based on the interactions found in the actual experimental structures we developed the first rule-based approach for predicting the ability of TCR residues in the complementarity-determining region (CDR) 1, CDR2, and CDR3 loops to interact with the MHC-peptide antigen complex. Two relatively simple algorithms show good performance under cross validation. [less ▲]

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See detailPPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome
Jurkowski, Wiktor UL; Roomp, Kirsten UL; Crespo, Isaac UL et al

in Cell Death & Disease (2011), 2(8), 192

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding ... [more ▼]

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network, the state of which can be shifted from the healthy to a stable diseased state. We found that a group of differentially expressed genes are involved in bi-stable switches and form a core network, the state of which changes with disease progression. These findings support the idea that bi-stable switches may be a mechanism for locking the core gene network into a diseased state and for efficiently propagating perturbations to more distant regions of the network. A structural analysis of the PPARγ-RXRα dimer complex supports the hypothesis of a major structural change between the two states, and this may represent an important mechanism leading to the differential expression observed in the core network. [less ▲]

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See detailHLA class I allele associations with HCV genetic variants in patients with chronic HCV genotypes 1a or 1b infection
Lange, Christian Markus; Roomp, Kirsten UL; Dragan, Anette et al

in Journal of Hepatology (2010), 53(6), 1022-1028

BACKGROUND & AIMS: The adaptive immune response against hepatitis C virus (HCV) is significantly shaped by the host's composition of HLA-alleles with the consequence that the HLA phenotype is a critical ... [more ▼]

BACKGROUND & AIMS: The adaptive immune response against hepatitis C virus (HCV) is significantly shaped by the host's composition of HLA-alleles with the consequence that the HLA phenotype is a critical determinant of viral evolution during adaptive immune pressure. In the present study, we aimed to identify associations of HLA class I alleles with HCV subtypes 1a and 1b genetic variants. METHODS: The association between HCV genetic variants and specific HLA-alleles was investigated in a cohort of 159 patients with chronic HCV genotypes 1a- and 1b-infection who were treated with pegylated interferon-alfa 2b and ribavirin in a prospective controlled trial for 48 weeks by direct sequencing of the genes encoding the HCV proteins E2, NS3, and NS5B and by HLA class I-genotyping of patients. HCV genetic variants were associated with specific HLA-alleles and the binding strength of accordant amino acid sequences to the corresponding HLA-allele was assessed by using the SYFPEITHI-algorithm. RESULTS: Overall, associations between HLA class I alleles and HCV sequence variation were rare. Five unknown HLA class I-associated viral genetic variations were identified, which in part affected the binding of predicted HCV CD8+ T cell epitopes to the respective HLA-allele. In addition, different patterns of HLA class I-allele/HCV sequence associations between the two subtypes were observed. CONCLUSIONS: We identified several unknown HLA class I-restricted HCV variants which in part impair binding to predicted HCV CD8+ T cell epitopes with remarkable differences between HCV subtypes 1a and 1b quasispecies. [less ▲]

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See detailPredicting MHC class I epitopes in large datasets
Roomp, Kirsten UL; Antes, Iris; Lengauer, Thomas

in BMC Bioinformatics (2010), 11(90), 1-2

BACKGROUND: Experimental screening of large sets of peptides with respect to their MHC binding capabilities is still very demanding due to the large number of possible peptide sequences and the extensive ... [more ▼]

BACKGROUND: Experimental screening of large sets of peptides with respect to their MHC binding capabilities is still very demanding due to the large number of possible peptide sequences and the extensive polymorphism of the MHC proteins. Therefore, there is significant interest in the development of computational methods for predicting the binding capability of peptides to MHC molecules, as a first step towards selecting peptides for actual screening. RESULTS: We have examined the performance of four diverse MHC Class I prediction methods on comparatively large HLA-A and HLA-B allele peptide binding datasets extracted from the Immune Epitope Database and Analysis resource (IEDB). The chosen methods span a representative cross-section of available methodology for MHC binding predictions. Until the development of IEDB, such an analysis was not possible, as the available peptide sequence datasets were small and spread out over many separate efforts. We tested three datasets which differ in the IC50 cutoff criteria used to select the binders and non-binders. The best performance was achieved when predictions were performed on the dataset consisting only of strong binders (IC50 less than 10 nM) and clear non-binders (IC50 greater than 10,000 nM). In addition, robustness of the predictions was only achieved for alleles that were represented with a sufficiently large (greater than 200), balanced set of binders and non-binders. CONCLUSIONS: All four methods show good to excellent performance on the comprehensive datasets, with the artificial neural networks based method outperforming the other methods. However, all methods show pronounced difficulties in correctly categorizing intermediate binders. [less ▲]

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See detailShort communication: selection of thymidine analogue resistance mutational patterns in children infected from a common HIV type 1 subtype G source
Däumer, M.; Awerkiew, S.; Aragon, S. S. et al

in AIDS Research and Human Retroviruses (2010), 26(3), 275-278

In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively). The ... [more ▼]

In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively). The mechanisms by which these pathways are selected are not fully understood. To investigate possible factors driving the selection of the TAMs, we analyzed the TAM patterns with regard to the respective treatment, viral load, and HLA in 18 children all infected from a common source of HIV-1 clade G virus and initially treated with zidovudine. The HIV reverse transcriptase sequences of 14/18 children carried at least one TAM. At first sampling date, the T215Y-linked pattern was observed in five cases and the T215F cluster was seen in nine. During the follow-up period, three patients changed their patterns. Children treated with identical NRTI combinations at the first sampling date developed different pathways. Under AZT/d4T therapies, an association was found between the HLA B*13 (in combination with HLA DRB1*0701) and the mutation T215Y. The mutation T215Y reverted in three out of four patients who discontinued AZT/d4T treatment. We speculate that in the context of these subtype G viruses, the development of the T215Y mutation may be strongly disfavored whereas the presence of HLA B*13 may counteract this effect and permit its development. [less ▲]

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See detailIntensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine
Roomp, Kirsten UL; Rand, Jacquie

in Journal of Feline Medicine and Surgery (2009), 11(8), 668-682

Human diabetic patients routinely self-adjust their insulin dose using a protocol and home monitoring, and perform equally well or outperform physician directed adjustments. The objective of this study ... [more ▼]

Human diabetic patients routinely self-adjust their insulin dose using a protocol and home monitoring, and perform equally well or outperform physician directed adjustments. The objective of this study was to report the outcome of home monitoring of diabetic cats by owners using a protocol aimed at achieving euglycaemia, using ultra-low carbohydrate diets (< or =10% metabolisable energy) and the insulin analogue glargine for >10 weeks and/or until remission was achieved. Fifty-five cats diagnosed with diabetes mellitus, whose owners joined the online German Diabetes-Katzen Forum, were included. An overall remission rate of 64% was achieved in the cohort. Significantly higher remission rates were observed if good glycaemic control was achieved soon after diagnosis: 84% for cats started on the protocol within 6 months of diagnosis went into remission, and only 35% for cats that began more than 6 months after diagnosis (P<0.001). Only one mild clinical hypoglycaemic episode occurred observed despite tight blood glucose control. In conclusion, intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. [less ▲]

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See detailEvaluation of intensive blood glucose control using glargine in diabetic cats
Roomp, Kirsten UL; Rand, J.S.

in Journal of Veterinary Internal Medicine (2008), 22(3), 790

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See detailThe somogyi effect is rare in diabetic cats managed using glargine and a protocol aimed at tight glycemic control
Roomp, Kirsten UL; Rand, J. S.

in Journal of Veterinary Internal Medicine (2008), 22(3), 790-791

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See detailFactors predictive of non-insulin dependence in diabetic cats initially treated with insulin
Roomp, Kirsten UL; Rand, J. S.

in Journal of Veterinary Internal Medicine (2008), 22(3), 791

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See detailSelective pressures of HLA genotypes and antiviral therapy on human immunodeficiency virus type 1 sequence mutation at a population level
Ahlenstiel, G.; Roomp, Kirsten UL; Daumer, M. et al

in Clinical and Vaccine Immunology (2007), 14(10), 1266-1273

The objective of this study was a comprehensive analysis of the immune-driven evolution of viruses of human immunodeficiency virus type 1 (HIV-1) clade B in a large patient cohort treated at a single ... [more ▼]

The objective of this study was a comprehensive analysis of the immune-driven evolution of viruses of human immunodeficiency virus type 1 (HIV-1) clade B in a large patient cohort treated at a single hospital in Germany and its implications for antiretroviral therapy. We examined the association of the HLA-A, HLA-B, and HLA-DRB1 alleles with the emergence of mutations in the complete protease gene and the first 330 codons of the reverse transcriptase (RT) gene of HIV-1, studying their distribution and persistence and their impact on antiviral drug therapy. The clinical data for 179 HIV-infected patients, the results of HLA genotyping, and virus sequences were analyzed using a variety of statistical approaches. We describe new HLA-associated mutations in both viral protease and RT, several of which are associated with HLA-DRB1. The mutations reported are remarkably persistent within our cohort, developing more slowly in a minority of patients. Interestingly, several HLA-associated mutations occur at the same positions as drug resistance mutations in patient viruses, where the viral sequence was acquired before exposure to these drugs. The influence of HLA on thymidine analogue mutation pathways was not observed. We were able to confirm immune-driven selection pressure by major histocompatibility complex (MHC) class I and II alleles through the identification of HLA-associated mutations. HLA-B alleles were involved in more associations (68%) than either HLA-A (23%) or HLA-DRB1 (9%). As several of the HLA-associated mutations lie at positions associated with drug resistance, our results indicate possible negative effects of HLA genotypes on the development of HIV-1 drug resistance. [less ▲]

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See detailArevir: A Secure Platform for Designing Personalized Antiretroviral Therapies Against HIV
Roomp, Kirsten UL; Beerenwinkel, Niko; Sing, Tobias et al

in Leser, U.; Naumann, F.; Eckman, B. (Eds.) Data Integration in the Life Sciences (2006)

Despite the availability of antiretroviral combination therapies, success in drug treatment of HIV-infected patients is limited. One reason for therapy failure is the development of drug-resistant genetic ... [more ▼]

Despite the availability of antiretroviral combination therapies, success in drug treatment of HIV-infected patients is limited. One reason for therapy failure is the development of drug-resistant genetic variants. In principle, the viral genomic sequence provides resistance information and could thus guide the selection of an optimal drug combination. In practice however, the benefit of this procedure is impaired by (1) the difficulty in inferring the clinically relevant information from the genotype of the virus and (2) the restricted availability of this information. We have developed a secure platform for collaborative research aimed at optimizing anti-HIV therapies, called Arevir. A relational database schema was designed and implemented together with a webbased user interface. Our system provides a basis for monitoring patients, decision- support, and computational analyses. Thus, it merges clinical, diagnostic and bioinformatics efforts to exploit genomic and patient therapy data in clinical practice. [less ▲]

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See detailComputational methods for the design of effective therapies against drug resistant HIV strains
Beerenwinkel, N.; Sing, T.; Lengauer, T. et al

in Bioinformatics (2005), 21(21), 3943-50

Summary: The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure ... [more ▼]

Summary: The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data. [less ▲]

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See detailABCA1 regulatory variants influence coronary artery disease independent of effects on plasma lipid levels
Zwarts, K. Y.; Clee, S. M.; Zwinderman, A. H. et al

in Clinical Genetics (2002), 61(2), 115-125

The authors have previously shown that individuals heterozygous for ABCA1 mutations have decreased high density lipoprotein cholesterol, increased triglycerides and an increased frequency of coronary ... [more ▼]

The authors have previously shown that individuals heterozygous for ABCA1 mutations have decreased high density lipoprotein cholesterol, increased triglycerides and an increased frequency of coronary artery disease (CAD), and that single nucleotide polymorphisms (SNPs) in the coding region of the ABCA1 gene significantly impact plasma lipid levels and the severity of CAD in the general population. They have now identified several SNPs in non-coding regions of ABCA1 which may be important for the appropriate regulation of ABCA1 expression (i.e. in the promoter, intron 1 and the 5′ untranslated region), and have examined the phenotypic effects of these SNPs in the REGRESS population. Out of 12 SNPs, four were associated with a clinical outcome. A threefold increase in coronary events with an increased family history of CAD was evident for the G-191C variant. Similarly, the C69T SNP was associated with a twofold increase in events. In contrast, the C-17G was associated with a decrease in coronary events and the InsG319 was associated with less atherosclerosis. For all these SNPs, the changes in atherosclerosis and CAD occurred without detectable changes in plasma lipid levels. These data suggest that common variation in non-coding regions of ABCA1 may significantly alter the severity of atherosclerosis, without necessarily influencing plasma lipid levels. [less ▲]

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See detailExpression and functional analyses of novel mutations of ATP-binding cassette transporter-1 in Japanese patients with high-density lipoprotein deficiency
Nishida, Y.; Hirano, K.; Tsukamoto, K. et al

in Biochemical and Biophysical Research Communications (2002), 290(2), 713-721

ATP-binding cassette transporter-1 (ABCA1) gene is mutated in patients with familial high-density lipoprotein deficiency (FHD). In order to know the molecular basis for FHD, we characterized three ... [more ▼]

ATP-binding cassette transporter-1 (ABCA1) gene is mutated in patients with familial high-density lipoprotein deficiency (FHD). In order to know the molecular basis for FHD, we characterized three different ABCA1 mutations associated with FHD (G1158A/A255T, C5946T/R1851X, and A5226G/N1611D) with respect to their expression in the passaged fibroblasts from the patients and in the cells transfected with themutated cDNAs. Fibroblasts from the all patients showed markedly decreased cholesterol efflux to apolipoprotein (apo)-Al. In the fibroblasts homozygous for G1158A/A255T, the immunoreactive mass of ABCA1 could not be detected, even when stimulated by 9-cisretinoic acid and 22-R- hydroxycholesterol. In the fibroblasts homozygous for C5946T/R1851X, ABCA1 mRNA was comparable. Because the mutant ABCA1 protein (R1851X) was predicted to lack the epitope for the antibody used, we transfected FLAG-tagged truncated mutant (R1851X/ABCA1-FLAG) cDNA into Cos-7 cells, showing that the mutant protein expression was markedly reduced. The expression of N1611D ABCA1 protein was comparable in both fibroblasts and overexpressing cells, although cholesterol efflux from the cells was markedly reduced. These data indicated that, in the three patients investigated, the abnormalities and dysfunction of ABCA1 occurred at the different levels, providing important information about the expression, regulation, and function of ABCA1. [less ▲]

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See detailTruncation mutations in ABCA1 suppress normal upregulation of full-length ABCA1 by 9-cis-retinoic acid and 22-R-hydroxycholesterol
Wellington, C. L.; Yang, Y. Z.; Zhou, S. et al

in Journal of Lipid Research (2002), 43(11), 1939-1949

Mutations in ABCA1 uniformly decrease plasma HDL-cholesterol (HDL-C) and reduce cholesterol efflux, yet different mutations in ABCA1 result in different phenotypic effects in heterozygotes. For example ... [more ▼]

Mutations in ABCA1 uniformly decrease plasma HDL-cholesterol (HDL-C) and reduce cholesterol efflux, yet different mutations in ABCA1 result in different phenotypic effects in heterozygotes. For example, truncation mutations result in significantly lower HDL-C and apoliprotein A-I (apoA-I) levels in heterozygotes compared with nontruncation mutations, suggesting that truncation mutations may negatively affect the wild-type allele. To specifically test this hypothesis, we examined ABCA1 protein expression in response to 9-cis-retinoic acid (9-cis-RA) and 22-R-hydroxycholesterol (22-R-OH-Chol) in a collection of human fibroblasts representing eight different mutations and observed that truncation mutations blunted the response to oxysterol stimulation and dominantly suppressed induction of the remaining full-length allele to 5–10% of wild-type levels. mRNA levels between truncation and nontruncation mutations were comparable, suggesting that ABCA1 expression was suppressed at the protein level. Dominant negative activity of truncated ABCA1 was recapitulated in an in vitro model using transfected Cos-7 cells. Our results suggest that the severe reduction of HDL-C in patients with truncation mutations may be at least partly explained by dominant negative suppression of expression and activity of the remaining full-length ABCA1 allele. [less ▲]

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See detailCommon genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease
Clee, S. M.; Zwinderman, A. H.; Engert, J. C. et al

in Circulation (2001), 103(9), 1198-1205

BACKGROUND: Low plasma HDL cholesterol (HDL-C) is associated with an increased risk of coronary artery disease (CAD). We recently identified the ATP-binding cassette transporter 1 (ABCA1) as the major ... [more ▼]

BACKGROUND: Low plasma HDL cholesterol (HDL-C) is associated with an increased risk of coronary artery disease (CAD). We recently identified the ATP-binding cassette transporter 1 (ABCA1) as the major gene underlying the HDL deficiency associated with reduced cholesterol efflux. Mutations within the ABCA1 gene are associated with decreased HDL-C, increased triglycerides, and an increased risk of CAD. However, the extent to which common variation within this gene influences plasma lipid levels and CAD in the general population is unknown. METHODS AND RESULTS: We examined the phenotypic effects of single nucleotide polymorphisms in the coding region of ABCA1. The R219K variant has a carrier frequency of 46% in Europeans. Carriers have a reduced severity of CAD, decreased focal (minimum obstruction diameter 1.81+/-0.35 versus 1.73+/-0.35 mm in noncarriers, P:=0.001) and diffuse atherosclerosis (mean segment diameter 2.77+/-0.37 versus 2.70+/-0.37 mm, P:=0.005), and fewer coronary events (50% versus 59%, P:=0.02). Atherosclerosis progresses more slowly in carriers of R219K than in noncarriers. Carriers have decreased triglyceride levels (1.42+/-0.49 versus 1.84+/-0.77 mmol/L, P:=0.001) and a trend toward increased HDL-C (0.91+/-0.22 versus 0.88+/-0.20 mmol/L, P:=0.12). Other single nucleotide polymorphisms in the coding region had milder effects on plasma lipids and atherosclerosis. CONCLUSIONS: These data suggest that common variation in ABCA1 significantly influences plasma lipid levels and the severity of CAD. [less ▲]

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