کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3296236 | 1209866 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Kruppel-Like Factor 6 Genotype Is Associated With Fibrosis in Nonalcoholic Fatty Liver Disease
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کلمات کلیدی
HSCαSMAKLF6NAFLDα-smooth muscle actin - اکتین عضله آلفا صافNonalcoholic fatty liver disease - بیماری کبدی چربی غیر الکلیHepatic stellate cells - سلولهای ستارهای کبدیbody mass index - شاخص توده بدنBMI - شاخص توده بدنیKrüppel-like factor 6 - عامل کریپول مانند 6relative quantity - مقدار نسبیpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازSingle nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتید
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The Kruppel-Like Factor 6 Genotype Is Associated With Fibrosis in Nonalcoholic Fatty Liver Disease The Kruppel-Like Factor 6 Genotype Is Associated With Fibrosis in Nonalcoholic Fatty Liver Disease](/preview/png/3296236.png)
چکیده انگلیسی
Background & Aims: Although nonalcoholic fatty liver disease (NAFLD) is increasingly common, only a minority of affected individuals develop fibrotic liver disease. Based on its role in liver growth and repair, we explored whether Kruppel-like factor 6 (KLF6) plays a role in NAFLD progression. Methods: KLF6 expression in 31 fibrosis scored NAFLD liver biopsy specimens was assessed by real-time polymerase chain reaction. Transfected minigene constructs were used to study the effect of a polymorphism, KLF6-IVS1-27G>A, that promotes KLF6 alternative splicing in vitro. We genotyped KLF6-IVS1-27G>A in 3 groups of patients (UK group 1, n = 306; Italian group 2, n = 109; trio group 3, n = 61 children and parents). Results: KLF6 expression was increased in association with increased steatosis, inflammation, and fibrosis in NAFLD livers. KLF6-IVS1-27G>A promoted alternative splicing of KLF6 and abrogated the up-regulation of both α-smooth muscle actin and collagen 1 in LX-2 cells. Group 1 genotyping identified KLF6-IVS1-27G>A in 44 of 306 (14.4%) patients. Notably, KLF6-IVS1-27G>A was associated significantly with milder NAFLD, with only 25% having more advanced fibrosis compared with 45% of wild-type (wt) individuals. This trend was confirmed in group 2. A linear regression analysis including all 415 patients, adjusted for age, sex, body mass index, and blood glucose level, confirmed that presence of the wt KLF6 allele was an independent predictor of fibrotic NAFLD. Furthermore, we have shown preferential transmission of the wt allele to children with fibrotic NAFLD. Conclusions: We report a functional polymorphism in the KLF6 gene associated with advanced NAFLD and believe further study of KLF6 may enhance our understanding of this disease process.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 135, Issue 1, July 2008, Pages 282-291.e1
Journal: Gastroenterology - Volume 135, Issue 1, July 2008, Pages 282-291.e1
نویسندگان
Luca Miele, Gary Beale, Gillian Patman, Valerio Nobili, Julian Leathart, Antonio Grieco, Marilena Abate, Scott L. Friedman, Goutham Narla, Elisabetta Bugianesi, Christopher P. Day, Helen L. Reeves,