Association of X‐prolyl aminopeptidase 1 rs17095355 polymorphism with biliary atresia in Thai children

Kaewkiattiyot, Sarannut; Honsawek, Sittisak; Vejchapipat, Paisarn; Chongsrisawat, Voranush; Poovorawan, Yong

doi:10.1111/j.1872-034x.2011.00870.x

Cited by 35 publications

(28 citation statements)

References 18 publications

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“…This SNP is located upstream of two genes expressed in the hepatobiliary system, XPNPEP1 , encoding X-Prolyl Aminopeptidase 1, and ADD3 , encoding an F-actin binding protein called adducin 3 (Citterio et al 2003; Ersahin et al 2005). Association with the same SNP was replicated in a Thai cohort ( p < 0.003) of 124 BA cases compared against 114 controls (Kaewkiattiyot et al 2011). Both of these investigations were conducted on Asian subjects and there has been no report of this association in other ethnic groups.…”

Section: Introductionmentioning

confidence: 80%

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Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

et al. 2013

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In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 × 10−3) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA.

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Section: Introductionmentioning

confidence: 80%

“…Two independent studies in Asian patients showed an association of 10q25.1 variants with BA (Garcia-Barcelo et al 2010; Kaewkiattiyot et al 2011). Our investigation of genotyped and imputed SNPs in this region indicates that the association to BA at this locus is also present in Caucasians.…”

Section: Discussionmentioning

confidence: 99%

Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

et al. 2013

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“…The epidemiological study was conducted on clinical specimens collected upon conclusion of routine examinations and stored as anonymous. Serum samples were obtained from healthy individuals from two previous studies (influenza and biliary atresia control group) [30,31]. Patient identifiers including personal information (name, address) and hospitalization number were removed from these samples to protect patient confidentiality.…”

Section: Methodsmentioning

confidence: 99%

Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations

et al. 2014

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BackgroundHuman enterovirus 71 (EV71) is an important pathogen caused large outbreaks in Asian-Pacific region with severe neurological complications and may lead to death in young children. Understanding of the etiological spectrum and epidemic changes of enterovirus and population’s immunity against EV71 are crucial for the implementation of future therapeutic and prophylactic intervention.ResultsA total of 1,182 patients who presented with the symptoms of hand foot and mouth disease (67.3%) or herpangina (HA) (16.7%) and admitted to the hospitals during 2008-2013 were tested for enterovirus using pan-enterovirus PCR targeting 5′-untranslated region and specific PCR for viral capsid protein 1 gene. Overall, 59.7% were pan-enterovirus positive comprising 9.1% EV71 and 31.2% coxsackievirus species A (CV-A) including 70.5% CV-A6, 27.6% CV-A16, 1.1% CV-A10, and 0.8% CV-A5. HFMD and HA occurred endemically during 2008-2011. The number of cases increased dramatically in June 2012 with the percentage of the recently emerged CV-A6 significantly rose to 28.4%. Co-circulation between different EV71 genotypes was observed during the outbreak. Total of 161 sera obtained from healthy individuals were tested for neutralizing antibodies (NAb) against EV71 subgenotype B5 (EV71-B5) using microneutralization assay. The seropositive rate of EV71-B5 was 65.8%. The age-adjusted seroprevalence for individuals was found to be lowest in children aged >6 months to 2 years (42.5%). The seropositive rate remained relatively low in preschool children aged > 2 years to 6 years (48.3%) and thereafter increased sharply to more than 80% in individuals aged > 6 years.ConclusionsThis study describes longitudinal data reflecting changing patterns of enterovirus prevalence over 6 years and demonstrates high seroprevalences of EV71-B5 NAb among Thai individuals. The rate of EV71 seropositive increased with age but without gender-specific significant difference. We identified that relative lower EV71 seropositive rate in early 2012 may demonstrate widely presented of EV71-B5 in the population before account for a large outbreak scale epidemic occurred in 2012 with due to a relatively high susceptibility of the younger population.

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“…70 This association was replicated in Thai ( n = 124) and US ( n = 171) patient cohorts. 71,72 Although the biological relevance of this SNP is not yet known, the differential hepatic expression of ADD3 in affected livers suggest that SNPs in ADD3 might serve as a susceptibility factor or disease modifier. 72 Further progress in the field will require comprehensive, whole-genome mutation surveys in a patient population that is precisely phenotyped and meets stringent criteria for adequate statistical analyses, followed by proof-of-principle experiments to explore the biological relevance of SNPs.…”

Section: Pathogenic Mechanisms Of Diseasementioning

confidence: 99%

Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

Asai

Miethke

Bezerra

2015

Nat Rev Gastroenterol Hepatol

233

223

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Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease.

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Association of X‐prolyl aminopeptidase 1 rs17095355 polymorphism with biliary atresia in Thai children

Abstract: The association between XPNPEP1 rs17095355 polymorphism and BA has been demonstrated, particularly with the T allele. We hypothesize that the XPNPEP1 rs17095355 polymorphism confers increased susceptibility to the disease.

Cited by 35 publications

References 18 publications

Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations

Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

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