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ANALYSIS OF LEVEL OF BILE OBSTRUCTION AND ITS ASSOCIATION WITH INCREASED CYP7A1 AND MIR33A EXPRESSION IN BILE ACID

Dr Muhammad Abdullah Haris, Dr Maimoona Riaz, Dr Nabila Anber

Introduction: Bile acids are synthesized from cholesterol exclusively in the liver. The rate of bile acid synthesis is mainly controlled by transcriptional regulation of cholesterol 7α-hydroxylase (CYP7A1), which encodes the rate-limiting enzyme in the classic bile acid synthesis pathway. Objectives of the study: The main objective of the study s to analyze the level of Bile Obstruction and its association with increased CYP7A1 and MIR33a expression in bile acid. Materials and Methods: This cross-sectional study was conducted in Lahore General Hospital during March 2018 to November 2018. The data comprises of 100 patients of both genders. Blood sample was drawn for the analysis of PCR. Expression levels of CYP7A1 and three bile acid hepatic transporters (Abcg5, Abcg8 and Ldlr) was carried out by quantitative real time PCR using RNA extracted from the rat livers. Using Trizol reagent (Invitrogen, Carlsbad, CA) total RNA was extracted from the livers of killed rats, according to manufacturer’s protocol with slight modifications. Results: The data was collected from 100 patients. An analysis of 7α-hydroxylase mRNA levels in the rat livers revealed marked increase in the expression of CYP7A1 in bile ligated rats while the non-ligated rats showed a lower expression level. It was also observed that the rats on high fat diet had (WD) had higher levels of CYP7A1 mRNA in livers than the ones on regular laboratory chow, both in ligated and non-ligated groups. Conclusion: It is concluded that in such times of impaired release of bile acids to intestine, secondary pathway may be activated. Ligated rats showed increased CYP7A1 levels while 27-hydroxylase in the serum of such rats was high as compared to non-ligated group.

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