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Genetic factors of susceptibility and of severity in primary biliary cirrhosis.

Abstract：

BACKGROUND/AIMS:In primary biliary cirrhosis (PBC), pathogenesis is influenced by genetic factors that remain poorly elucidated up to now. We investigated the impact of sequence diversity in candidate genes involved in immunity (CTLA-4 and TNFalpha), in bile formation (10 hepatobiliary transporter genes) and in the adaptative response to cholestasis (three nuclear receptor genes) on the susceptibility and severity of PBC. METHODS:A total of 42 Ht SNPs were identified and compared in 258 PBC patients and two independent groups of 286 and 269 healthy controls. All participants were white continental individuals with French ancestry. RESULTS:Ht SNPs of CTLA-4 and TNFalpha genes were significantly associated with susceptibility to PBC. The progression rate of liver disease under ursodeoxycholic acid (UDCA) therapy was significantly linked to SNPs of TNFalpha and SLC4A2/anion exchanger 2 (AE2) genes. A multivariate Cox regression analysis including clinical and biochemical parameters showed that SLC4A2/AE2 variant was an independent prognostic factor. CONCLUSIONS:These data point to a primary role of genes encoding regulators of the immune system in the susceptibility to PBC. They also demonstrate that allelic variations in TNFalpha and SLC4A2/AE2 have a significant impact on the evolutive profile of PBC under UDCA therapy.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Poupon R,Ping C,Chrétien Y,Corpechot C,Chazouillères O,Simon T,Heath SC,Matsuda F,Poupon RE,Housset C,Barbu V

doi

10.1016/j.jhep.2008.07.027

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

1038-45

issue

6

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(08)00602-8

journal_volume

49

pub_type

杂志文章

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