Linkage of Graves' disease to the human leucocyte antigen region in the Chinese-Han population in Taiwan

Objective: To investigate whether markers in the candidate chromosome regions, including the human leucocyte antigen (HLA) region, are linked to Graves' disease (GD). Design: A familial linkage study with a candidate region approach. Patients: 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. Measurements: 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. ? 2007 The Authors.