Prevalence of mutations in MDR3/ABCB4 gene in young patients with cholelithiasis.

Radha, M (2013) Prevalence of mutations in MDR3/ABCB4 gene in young patients with cholelithiasis. Masters thesis, Madras Medical College, Chennai.


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INTRODUCTION : Bile is secreted from the hepatocyte and it is essential for lipid metabolism, excretion of xenobiotic, and cholesterol homeostasis. Bile secretion depends upon the formation of bile acids in hepatocyte and its canalicular secretion.Once secreted in to the bile duct, bile enters the small bowel through the ampulla of water during the digestion phase. Bile stored inside the gall bladder during inter- digestive phase. After reaching the small bowel, the bile acid isabsorbed in the terminal ileum, and undergoesthe enterohepatic cycling. This happens 5-6 times per day and maintains the bile acid pool. This is essential to maintain the normal liver function. Gall stones are formed when ever alteration in the chemical composition. Disturbance in bile acid formation,canalicular secretion and intestinal transport leads to gall stone it is important to identify hepatic, biliary, and intestinal bile acid transporters in the bile formation and secretion. Gall stones divided into three types: (1) Cholesterol Stones, (2) Pigment Stones-(black), (3) Pigment Stones - (brown). Cholesterol stones are more common in north India in compare with southern India where pigment and mixed stones are common. Most of the gall stones are asymptomatic in presentation. The exact role of genetics in the formation of gallstones still not understood. The prevalence varies between the ethnic groups. ABCB4 – encoding for the ATP-binding cassette, member of MDR3. It mediates the efflux of phospholipids from hepatocytes into canaliculi mainly the phosphatidylcholine [PC] into the bile. The function of phospholipid excretion is to protect the cell membrane from toxic bile saltsin the biliary tree.When function isdefective, it produces the spectrum of disorders, ranges from cholestasis, Cholelithiasis, Intrahepatic Cholestasis of Pregnancy, Ductopenia, and Cirrhosis. So when ever other risk factors exclude for the formation of gall stone disease still the possibility of genetic transporters defect. When mutation occurs at ABCB4 gene, causes the low phospholipid and high lithogenic bile. Hence in this study we are looking for the prevalence of mutations in MDR3/ABCB4 gene in young patients with Cholelithiasis. AIM OF THE STUDY : To study and analyze the clinical profile, association of mutations in the MDR3/ABCB4 in young patients age less than 40 years with Cholelithiasis. CONCLUSION : This is first study to screen variations in ABCB4 gene in young patients with gall stones in India. Mutation can be spread along entire length of the gene. We could not find any mutation in Exon 17 of ABCB4. Gene.An intronic variation in g.51576C>T in intron 17 was observed in our patients. This implies that this mutation can have functional defects in the action of proteins leading to lithogenic bile, larger studies covering all the exons of ABCB4 gene might throw more light in genetics of this transporter defects in Indian Population. If a mutation can demonstrated in these patients might benefitnfrom lifelong UDCA therapy decrease the lithogenicity of bile.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Prevalence of mutations ; MDR3/ABCB4 gene ; young patients ; cholelithiasis.
Subjects: MEDICAL > Gastroenterology
Depositing User: Kambaraman B
Date Deposited: 13 Jul 2017 04:10
Last Modified: 13 Jul 2017 04:10

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