کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6806312 1433572 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Alzheimer's disease susceptibility variants in the MS4A6A gene are associated with altered levels of MS4A6A expression in blood
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Alzheimer's disease susceptibility variants in the MS4A6A gene are associated with altered levels of MS4A6A expression in blood
چکیده انگلیسی
Common variants located within highly expressed MS4A6A transcripts were significantly associated with AD and MS4A6A expression levels in blood from MCI and AD subjects (p < 0.05, rs610932, rs7232, rs583791). More copies of the protective (minor) allele were associated with lower MS4A6A expression of each transcript (e.g., p = 0.019; rs610932-total MS4A6A). Furthermore, in heterozygous AD subjects, relative expression of the protective allele of V4-MS4A6A transcripts was lower (p < 0.008). Irrespective of genotype, MS4A6A transcripts were increased in blood from people with AD (p < 0.003), whereas lower expression of full length V1-MS4A6A (p = 0.002) and higher expression of V4-MS4A6A (p = 1.8 × 10−4) were observed in MCI, relative to elderly controls. The association between genotype and expression was less consistent in brain, although BA9 did have a similar genotype association with V4-MS4A6A transcripts as in blood. MS4A6A transcripts were widely expressed in tissues and cells, with the exception of V4-MS4A6A, which was not expressed in neuronal cells. Together these results suggest that high levels of MS4A6A in emerging AD pathology are detrimental. Persons with MCI may lower MS4A6A expression to minimize detrimental disease associated MS4A6A activity. However, those with the susceptibility allele appear unable to decrease expression sufficiently, which may explain their increased risk for developing AD. Inhibiting MS4A6A may therefore promote a more neuroprotective phenotype, although further work is needed to establish whether this is the case.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 35, Issue 2, February 2014, Pages 279-290
نویسندگان
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