| 1. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 2. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 3. |
- Al-Hashimi, Ibtisam, et al.
(författare)
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Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations.
- 2007
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Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1528-395X .- 1079-2104. ; 103 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- Several therapeutic agents have been investigated for the treatment of oral lichen planus (OLP). Among these are corticosteroids, retinoids, cyclosporine, and phototherapy, in addition to other treatment modalities. A systematic review of clinical trials showed that particularly topical corticosteroids are often effective in the management of symptomatic OLP lichen planus. Systemic corticosteroids should be only considered for severe widespread OLP and for lichen planus involving other mucocutaneous sites. Because of the ongoing controversy in the literature about the possible premalignant character of OLP, periodic follow-up is recommended. There is a spectrum of oral lichen planus-like ("lichenoid") lesions that may confuse the differential diagnosis. These include lichenoid contact lesions, lichenoid drug reactions and lichenoid lesions of graft-versus-host disease. In regard to the approach to oral lichenoid contact lesions the value of patch testing remains controversial. Confirmation of the diagnosis of an oral lichenoid drug reaction may be difficult, since empiric withdrawal of the suspected drug and/or its substitution by an alternative agent may be complicated. Oral lichenoid lesions of graft-versus-host disease (OLL-GVHD) are recognized to have an association with malignancy. Local therapy for these lesions rests in topical agents, predominantly corticosteroids.
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| 4. |
- Assimes, Themistocles L., et al.
(författare)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 5. |
- Brennan, Michael, et al.
(författare)
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Management of oral epithelial dysplasia: a review.
- 2007
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Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1528-395X .- 1079-2104. ; 103 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- One of the goals of the fourth meeting of The World Workshop on Oral Medicine (WWOM IV) included a review of the pathophysiology and future directions for the clinical management of patients with oral epithelial dysplasia, excluding the lips and oropharynx. In the pathophysiology review of dysplasia since WWOM III (1998-2006), a wide range of molecular changes associated with progression of dysplasia to squamous cell carcinoma were found. These include loss of heterozygosity, dysregulation of apoptosis, aberrant DNA expression, and altered expression of numerous tissue markers. Based on the literature search, no single molecular pathway has been identified as the primary factor in progression of dysplasia to squamous cell carcinoma. A systematic review of medical (i.e., nonsurgical) management strategies for the treatment of dysplastic lesions has shown promising results in short-term resolution of dysplasia in the small number of studies that met eligibility criteria for review. However, because of the limited periods of follow-up reported in these studies, it remains unclear as whether resolution of dysplasia would actually be a long-term benefit of these interventions. This question is particularly germane when it is considered in the context of prevention of future development of squamous cell carcinoma. Because of the lack of randomized controlled trials that have shown effectiveness in the prevention of malignant transformation, no recommendations can be provided for specific surgical interventions of dysplastic oral lesions either.
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| 6. |
- Elad, Sharon, et al.
(författare)
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Topical immunomodulators for management of oral mucosal conditions, a systematic review; part I: calcineurin inhibitors.
- 2010
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Ingår i: Expert opinion on emerging drugs. - : Informa Healthcare. - 1744-7623 .- 1472-8214. ; 15:4, s. 713-26
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Tidskriftsartikel (refereegranskat)abstract
- Topical immunomodulators have been used for the management of oral mucosal diseases. Topical immunomodulating preparations may have utility in local management of oral disease which is resistant to topical steroids and oral findings of an immunologic-mediated systemic disease with primary or persisting, oral mucosal involvement.
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| 7. |
- Elad, Sharon, et al.
(författare)
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Topical immunomodulators for management of oral mucosal conditions, a systematic review; Part II: miscellaneous agents.
- 2011
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Ingår i: Expert opinion on emerging drugs. - : Informa Healthcare. - 1744-7623 .- 1472-8214. ; 16:1, s. 183-202
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Topical immunomodulating preparations have utility in inflammatory/immune-mediated oral mucosal disease resistant to topical steroids, in immunologically mediated systemic disease with primary oral involvement or more severe lesions primarily involving the oral mucosa. AREAS COVERED: This paper is the second part of a systematic review of a variety of topical immunomodulators for management of immune/inflammatory oral mucosal conditions. The literature search revealed studies of azathioprine, benzydamine, GM-CSF and G-CSF, tetracyclines, retinoids, imiquimod, amlexanox, sirolimus and bacillus Calmette-Guerin polysaccharide nucleic acid. Weighted conclusions are provided for the topical use of each of the immunomodulators reviewed in the management of these oral diseases. EXPERT OPINION: Topical immunomodulators may be useful as second line treatment in several oral diseases, particularly oral lichen planus and recurrent aphthous stomatitis. Benzydamine was found to be preventive in radiotherapy-induced mucositis; however, it is unclear if this outcome is related to its immunomodulating effects or other mechanisms of action. Topical application of tetracyclines and retinoic acid also shows potential anti-inflammatory actions.
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