کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6810120 | 1433599 | 2012 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Association and heterogeneity at the GAPDH locus in Alzheimer's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogs were implicated in late-onset Alzheimer's disease (LOAD), although the strength and direction of association have not been consistent. We genotyped 3 previously reported single nucleotide polymorphisms (SNPs; rs3741916-GAPDH 5â² UTR, rs2029721-pGAPD, and rs4806173-GAPDHS) in 3 case-control series (2112 cases and 3808 controls). Rs3741916 showed the strongest LOAD association (p = 0.003). The minor allele of rs3741916 showed a protective effect in our combined series (odds ratio [OR] = 0.87%, 95% confidence interval [CI] = 0.79-0.96). This is consistent with results from the 2 published follow-up studies and in opposite direction of the original report. Meta-analysis of the published series with ours suggests presence of heterogeneity (Breslow-Day p < 0.0001). Meta-analysis of only the follow-up series including ours revealed a significant protective effect for the minor allele of rs3741916 (OR = 0.85%, 95% CI = 0.76-0.96, p = 0.009). Our results support the presence of LOAD variants and heterogeneity at the GAPDH locus. The most promising rs3741916 variant is unlikely to be functional given opposing effects in different series. Identification of functional variant(s) in this region likely awaits deep sequencing.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 33, Issue 1, January 2012, Pages 203.e25-203.e33
Journal: Neurobiology of Aging - Volume 33, Issue 1, January 2012, Pages 203.e25-203.e33
نویسندگان
Mariet Allen, Claire Cox, Olivia Belbin, Li Ma, Gina D. Bisceglio, Samantha L. Wilcox, Chanley C. Howell, Talisha A. Hunter, Oliver Culley, Louise P. Walker, Minerva M. Carrasquillo, Dennis W. Dickson, Ronald C. Petersen, Neill R. Graff-Radford,