کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3297914 | 1209891 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional Variants of the Central Bile Acid Sensor FXR Identified in Intrahepatic Cholestasis of Pregnancy
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کلمات کلیدی
GGTDBDICPSHPECRFXRUSPUltraspiraclefarnesoid X receptor - Farnesoid X گیرندهγ-glutamyl transpeptidase - γ-گلوتامیل ترانسپپتیدازDNA-Binding Domain - دامنه اتصال DNApolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازIntrahepatic cholestasis of pregnancy - کلستاز داخل شکمی بارداریshort heterodimer partner - کوتاه همکارEcdysone receptor - گیرنده اگزایسون
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Functional Variants of the Central Bile Acid Sensor FXR Identified in Intrahepatic Cholestasis of Pregnancy Functional Variants of the Central Bile Acid Sensor FXR Identified in Intrahepatic Cholestasis of Pregnancy](/preview/png/3297914.png)
چکیده انگلیسی
Background & Aims: Intrahepatic cholestasis of pregnancy (ICP) is characterized by liver impairment, pruritus, and elevated maternal serum bile acids. It can cause premature delivery and intrauterine death. Bile acid synthesis, metabolism, and transport are regulated by the bile acid sensor FXR, and we hypothesized that genetic variation in FXR confers susceptibility to ICP. Methods: The coding regions and intron/exon boundaries of FXR were sequenced in 92 British ICP cases of mixed ethnicity. Subsequently, a case-control study of allele frequencies of these variants in 2 independent cohorts of Caucasian ICP patients and controls was performed. Variants were cloned into an FXR expression plasmid and tested in functional assays. Results: We identified 4 novel heterozygous FXR variants (â1g>t, M1V, W80R, M173T) in ICP. W80R was not present in Caucasians and M1V was detected uniquely in 1 British case. M173T and â1g>t occur both in Caucasian cases and controls, and we found a significant association of M173T with ICP (OR, 3.2; 95% confidence interval, 1.1-11.2; P = .02) when the allele frequencies of both Caucasian cohorts were analyzed together. We demonstrate functional defects in either translation efficiency or activity for 3 of the 4 variants (â1g>t, M1V, M173T). Conclusions: This is the first report of functional variants in FXR. We propose that these variants may predispose to ICP, and because FXR has a central role in regulating bile and lipid homeostasis they may be associated with other cholestatic and dyslipidemic disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 133, Issue 2, August 2007, Pages 507-516
Journal: Gastroenterology - Volume 133, Issue 2, August 2007, Pages 507-516
نویسندگان
Saskia W.C. van Mil, Alexandra Milona, Peter H. Dixon, Roman Mullenbach, Victoria L. Geenes, Jenny Chambers, Vasylyna Shevchuk, Gudrun E. Moore, Frank Lammert, Anna G. Glantz, Lars-Ã
ke Mattsson, John Whittaker, Malcolm G. Parker, Roger White,