葛瑞夫茲氏病基因研究-以家族為基礎之關聯研究（2/3）
Date Issued
2004
Date
2004
Author(s)
張天鈞
DOI
923112B002009
Abstract
Graves’ disease (GD), a common organ-specific autoimmune disorder with clinical importance, is
a multifactorial disease and develops in genetically susceptible individuals. Despite much effort
during the past decade, the susceptibility genes of GD are still uncertain. The cytotoxic T
lymphocyte antigen-4 (CTLA4) is an important negative regulator of antigen-activated immune
response, and is among the most possible susceptibility genes of GD. However, up to now, none
of family-based studies in non-Caucasian populations show linkage or association between
CTLA4 and GD. To search for the susceptibility genes of GD, and to clarify the role of CTLA4 to
GD outside Caucasian population, we conducted this study in Chinese-Han pedigrees in Taiwan.
We enrolled 403 affected and 274 unaffected individuals in 171 pure GD families, which is the
single largest family dataset in the world. As a candidate gene approach, we typed 9
microsatellite markers spanning 24 cM around CTLA4 gene, and 7 SNP markers. Non-parametric
linkage analysis peaked around CTLA4 with a multipoint NPL score of 1.57 (P = 0.047).
Family-based association test demonstrated association with GD at a promoter region SNP
(P=0.031) and the promoter-to-exon 1 haplotype (P=0.029). Our results support that CTLA4 is
both linked to and associated with GD in Chinese-Han population in Taiwan. Currently, we are
performing functional study of the different haplotypes of CTLA4 gene. In addition, we are also
carrying on linkage and association study of other candidate regions and genes, including
5q31-q33, pendrin gene (7q31), HLA region (6p), thyrostimulin region (14q31) and other
immune related genes.
Subjects
Graves’ disease
gene
family-based studies
Chinese-Han
linkage analysis
association study
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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