title: Linkage of Graves' disease to the human leucocyte antigen region in the Chinese-Han population in Taiwan.
abstract: OBJECTIVE
  To investigate whether markers in the candidate chromosome regions, including the human leucocyte antigen (HLA) region, are linked to Graves' disease (GD).
  
  
  METHODS
  A familial linkage study with a candidate region approach.
  
  
  METHODS
  A total of 536 individuals in 122 multiplex Chinese-Han families with a GD proband and at least one other affected sibling, resulting in 270 affected sib-pairs. Subjects with a family history of noniatrogenic hypothyroidism or Hashimoto's thyroiditis were excluded.
  
  
  METHODS
  We genotyped eight short tandem repeat polymorphism (STRP) markers in a 13.7 cM region covering the HLA region on chromosome 6p21 and 26 STRPs in four other candidate regions previously reported in the literature.
  
  
  RESULTS
  Multipoint nonparametric linkage (NPL) analysis showed significant linkage to the HLA region [the marker UniSTS:239159, nonparametric log of odds (LOD) score 3.44, P = 0.00003; NPL Z-score 4.1, P = 0.00002] from 270 affected sib-pairs. The 1-LOD support interval comprised the whole HLA region (ca. 4 Mb). By contrast, the maximal NPL Z-scores of the markers of the other candidate regions (2q33, 5q31, 7q22 and 14q31) previously reported were all less than 1.0.
  
  
  CONCLUSIONS
  Our results provide strong support for linkage of GD to the HLA region. Further dissection of this region to identify the candidate gene for GD is warranted in our population.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Lung
authors.initials: PL
authors.lastname: Chen
authors.forename: Cathy Shen-Jang
authors.initials: CS
authors.lastname: Fann
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Chang
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Wu
authors.forename: Wei-Yih
authors.initials: WY
authors.lastname: Chiu
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Tien-Chun
authors.initials: TC
authors.lastname: Chang
mesh_terms: D044466:Asian People; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008126:Lod Score; D008285:Major Histocompatibility Complex; D008297:Male; D018895:Microsatellite Repeats; D013624:Taiwan
chemical_list: D005819:Genetic Markers