Circulating microRNA is a biomarker of biliary atresia.
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ABSTRACT:
SUBMITTER: Zahm AM
PROVIDER: S-EPMC3459263 | biostudies-literature | 2012 Oct
REPOSITORIES: biostudies-literature
Publications
Circulating microRNA is a biomarker of biliary atresia.
Zahm Adam M AM Hand Nicholas J NJ Boateng LaTasha A LA Friedman Joshua R JR
Journal of pediatric gastroenterology and nutrition 20121001 4
<h4>Objective</h4>The lack of reliable noninvasive diagnostic biomarkers of biliary atresia (BA) results in delayed diagnosis and worsened patient outcome. Circulating microRNAs (miRNAs) are a new class of noninvasive biomarkers with encouraging diagnostic utility.<h4>Methods</h4>We examined the ability of serum miRNAs to distinguish BA from other forms of neonatal hyperbilirubinemia. BA-specific serum miRNAs were identified using a microfluidic array platform and validated in a larger, independ ...[more]
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Project description:Aim of the studyWe aimed to evaluate the association of microRNA-499 rs3746444 polymorphism and biliary atresia (BA) risk and its correlation with clinic-pathologic features of BA.Material and methodsThis study was performed on 300 Egyptian children (100 BA cases, 100 cases with cholestatic liver diseases other than BA and 100 healthy controls). Routine laboratory investigations, clinical examination and abdominal ultrasound were done. All infants were genotyped for miR-499 single nucleotide polymorphisms (SNPs) (rs3746444 A>G) by real-time polymerase chain reaction (PCR) fluorescence detection on a Rotor Gene Real Time PCR System (QIAGEN, GmbH) using fluorescent labeled probes.ResultsThe AG genotype was the most prevalent genotype of miR-499 rs3746444 among the studied groups. A significantly higher frequency of the rs3746444 G allele was found in the BA cases than the other groups (odds ratio = 1.62). This polymorphism was also correlated with the degree of fibrosis in BA cases (p < 0.05). The miR-499 rs3746444 polymorphism (GG genotype) was significantly associated with severe form of BA and bad prognosis after the Kasai operation (p < 0.05). miR-499 rs3746444 polymorphism had no effect on the clinic-pathological features or the liver function status in the non-BA group.ConclusionsThere is an association between the miR-499 SNP genotypes and the occurrence of BA. The variant allele G is the predominant allele in the BA group and is associated with severe liver inflammation and bad prognosis after the Kasai operation.
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Project description:ObjectiveBiliary atresia (BA) is the most common cause of neonatal jaundice, characterized by progressive and rapid liver fibrosis. Recent studies have shown that microRNAs (miRNAs) contribute to the liver fibrogenesis. We investigated the miRNA-21 impact in liver fibrogenesis in Indonesian BA patients.ResultsThere were 5, 4, and 7 BA patients with type 2A, 2B, and 3, respectively. Quantitative real-time polymerase chain reaction (qPCR) showed that the miRNA-21 expression was significantly increased (18-fold) in BA patients compared to controls (- 4.4 ± 4.0 vs. - 0.2 ± 4.8; p = 0.041). Furthermore, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression was significantly down-regulated (3.1-fold) in BA group compared to control group (0.2 ± 1.4 vs. - 1.4 ± 1.7; p = 0.036). The α-smooth muscle actin (α-SMA) expression was not statistically significantly different between groups (13.7 ± 3.8 vs. 15.0 ± 4.8; p = 0.87). Interestingly, the miRNA-21 expression was significantly lower (25-fold) in cirrhosis than non-cirrhosis BA patients (- 0.8 ± 2.2 vs. - 5.3 ± 3.9; p = 0.004). In conclusions, our study provides support for the association between miRNA-21 expression and liver cirrhosis in BA patients. Further study with a larger sample size of patients is important to confirm our results.
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Project description:The treatment of biliary atresia (BA) is predominantly surgical with firstly an attempt at restoration of bile flow from the native liver by wide excision of the obstructed, obliterated extrahepatic biliary tree to the level of the porta hepatis and a portoenterostomy using a long Roux loop-Kasai portoenterostomy (KPE). Liver transplantation is reserved for those that fail this and for those where surgery is considered futile for reasons of age or stage of disease. As the aetiology of BA remains ill-defined, so adjuvant treatment has been largely based on pragmatism, trial and error. Systematic analysis of the few randomized placebo-controlled trial data and less well-controlled cohort studies have suggested benefit from post-operative high-dose steroids and ursodeoxycholic acid (UDCA) while the benefit of long-term prophylactic antibiotics, bile acid sequestrants (e.g., colestyramine) or probiotics remains unproven. Newer modalities such as antiviral therapy (AVT), immunoglobulin, FXR agonists (e.g., obeticholic acid), ileal bile acid transporter (IBAT) antagonists (e.g., maralixibat) remain unproven. This article reviews the current evidence for the efficacy of adjuvant medical therapy in BA.
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