title: A genomewide DNA microsatellite association study of Japanese patients with autoimmune hepatitis type 1.
abstract: Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA class II genes. We previously searched the whole HLA region for AIH susceptibility genes using microsatellite markers and found only HLA-DR/DQ to be a candidate region for this suspected multifactorial disease. As such, the aim of this study was to broaden our search and screen the whole genome for additional genes that might contribute to type 1 AIH susceptibility. Eighty-one patients with type 1 AIH (15 men, 66 women, average age 55.9) and 80 healthy sex- and age-matched Japanese controls were enrolled in this study. We performed a case-control association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. Two markers, one on chromosome 11 (D11S902, Pc = 0.013) and one on chromosome 18 (D18S464, Pc = 0.008), were revealed to have statistically significant associations with AIH. An additional 7 markers (D2S367, D6S309, D9S273, D11S1320, D16S423, D17S938, and D18S68) were also found to be candidate susceptibility regions. In addition, our results showed there were 17 regions that may contain genes of resistance to AIH. No specific markers were detected in HLA-DR4-negative patients, and no differences were seen in the clinical courses of patients (severe versus mild to moderate).
  
  
  CONCLUSIONS
  This first genomewide scan of Japanese AIH patients revealed at least 26 candidate AIH susceptibility or resistance regions other than HLA class II loci. These results also suggested that the products of several genes interact to determine heritable susceptibility to AIH.
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yokosawa
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ichijo
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D015894:Genome, Human / Q000235:genetics*; D019693:Hepatitis, Autoimmune / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D004247:DNA