کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2894145 1172428 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A commonly occurring polymorphism upstream of the estrogen receptor alpha alters transcription and is associated with increased HDL
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
A commonly occurring polymorphism upstream of the estrogen receptor alpha alters transcription and is associated with increased HDL
چکیده انگلیسی

ObjectiveGiven the role of estrogen in the regulation of lipid metabolism, we screened for functional polymorphisms in the estrogen receptor alpha (ERα), and examined for their influence on serum cholesterol.Methods and resultsWe identified a novel C > T polymorphism (ERNE-145), with a minor allele frequency of 41%. This polymorphism was immediately adjacent to a putative glucocorticoid receptor (GR) binding site, which we showed to be functional by electrophoretic mobility shift analysis. The C allele was associated with glucocorticoid-induced reduction in promoter activity compared to control in luciferase reporter studies (p < 0.05; n = 7). This effect was abolished by the T allele. To investigate the functional significance of ERNE-145, its association with serum cholesterol levels was examined in 1662 post-menopausal women enrolled in the RUTH trial. ERNE-145 genotype (p = 0.001), BMI (p < 0.001), diabetes mellitus (p < 0.001), and ethnicity (p = 0.002) were significantly associated with HDL cholesterol. ERNE-145 genotype explained 8.2% of the variability of HDL: each copy of the variant T allele was associated with a 0.041 mmol/L (CI 0.017–0.066) increase in HDL.ConclusionA novel polymorphism upstream of ERα abolished negative transcriptional regulation by an adjacent GR binding sequence, and was strongly associated with HDL levels in a large cohort of post-menopausal women.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 199, Issue 2, August 2008, Pages 354–361
نویسندگان
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