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Circulating mitochondrial DNA content associated with the risk of liver cirrhosis: a nested case-control study.

Abstract：

BACKGROUND AND AIMS:Accumulating evidence has indicated that variations of mitochondrial DNA (mtDNA) content may affect the susceptibility to hepatocellular carcinoma (HCC). However, no study has been conducted to evaluate the association of circulating mtDNA content and the risk of liver cirrhosis, a leading cause of HCC. METHODS:We conducted a nested case-control study including 136 cirrhotic hepatitis B virus (HBV) cases and 136 frequency-matched non-cirrhotic HBV controls. We determined mtDNA content in serum DNA using quantitative real-time PCR and analyzed its association with cirrhosis risk. RESULTS:We found that cirrhotic HBV patients had significantly lower levels of mtDNA content than non-cirrhotic HBV controls (P = 0.0184). Compared to patients with high mtDNA content, those with low mtDNA content had a 2.25-fold increased risk of cirrhosis [odds ratio (OR) 2.25, 95 % confidence interval (CI) 1.26-4.02]. This association exhibited a significant dose relationship as evidenced in both tertile and quartile analyses (P for trend = 0.0018 and 0.0008, respectively). Stratified analyses showed that the association was prominent in younger patients (P = 0.0122), males (P = 0.0069), never smokers (P = 0.0063), never drinkers (P = 0.0078), patients with a family history of HBV infection (P = 0.0062), and patients with low values of aspartate aminotransferase to platelet ratio index (APRI), a commonly used noninvasive marker for cirrhosis (P = 0.0109). Moreover, a joint effect was observed between low mtDNA content and high APRI values on cirrhosis risk (OR 24.07, 95 % CI 6.72-86.24). CONCLUSIONS:Low circulating mtDNA content may confer an increased cirrhosis risk in HBV patients. Further prospective studies are warranted to validate these findings and explore the clinical significance.

journal_name

Dig Dis Sci

journal_title

Digestive diseases and sciences

authors

Wang C,Hann HW,Hann RS,Wan S,Myers RE,Ye Z,Xing J,Yang H

doi

10.1007/s10620-015-3523-1

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1707-15

issue

eissn

0163-2116

issn

1573-2568

journal_volume

pub_type

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Circulating mitochondrial DNA content associated with the risk of liver cirrhosis: a nested case-control study.