title: High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease.
abstract: OBJECTIVE
  Alpha-1-antitrypsin (A1AT) deficiency is the most common genetic cause of liver disease in children; however, the role of polymorphic heterogeneity in the A1AT gene as a modifier of other forms of pediatric liver disease is not clear. We hypothesized that non-M A1AT allele variants are more common in children with chronic liver disease than in the general population.
  
  
  METHODS
  A retrospective, single-center study was performed in which A1AT phenotypes were obtained by reviewing charts of children with chronic liver disease. Chi-square analysis was used to compare allele frequencies in the population of children with liver disease with published epidemiologic data and to compare allele frequencies among disease subgroups.
  
  
  RESULTS
  The frequency of A1AT Z and other alleles was increased in children with chronic liver disease (n = 241) when compared with the published reference database (P < 0.001). This increase remained significant when the population was divided into disease subsets: biliary atresia (n = 67) and other liver disease (n = 174) (P < 0.001 for both). Among children with biliary atresia referred for liver transplant evaluation, the presence of a non-M allele was associated with a lower mean age at transplant listing than the MM phenotype (235 vs 779 days, P = 0.036) and more frequent loss of native liver by 24 months of age (90% vs 65%, P = 0.04).
  
  
  CONCLUSIONS
  A1AT non-M alleles are more frequent in children with chronic liver disease than in the general population. We speculate that these non-M alleles may act as genetic modifiers in pediatric liver disease in general and modulate disease progression in children with biliary atresia in particular.
authors.affiliation: Pediatric Liver Care Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. kathleen.campbell@cchmc.org
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Campbell
authors.forename: Gajra
authors.initials: G
authors.lastname: Arya
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Ryckman
authors.forename: Maria
authors.initials: M
authors.lastname: Alonso
authors.forename: Greg
authors.initials: G
authors.lastname: Tiao
authors.forename: William F
authors.initials: WF
authors.lastname: Balistreri
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Bezerra
mesh_terms: D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008107:Liver Diseases / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D000515:alpha 1-Antitrypsin