Family-based association study of cytotoxic T-lymphocyte antigen-4 with susceptibility to Graves' disease in Han population of Taiwan.
Graves' disease (GD) is a common organ-specific autoimmune disorder inherited as a complex trait. Although there has not been consensus regarding the genuine susceptibility alleles, many population-based genetic studies showed association of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene with GD. In contrast, evidence utilizing family-based studies came only from the Caucasian population. Here we performed a family-based association study in the Han population in Taiwan. We enrolled 374 affected individuals and 347 unaffected family members in 151 GD pedigrees. Four single-nucleotide polymorphisms (SNP) and a short tandem repeat polymorphism (STRP) at CTLA4 were genotyped. Association of GD with a novel risk SNP at the 5' upstream region, CTLA4_-1722_T/C (rs733618), was demonstrated (P=0.0096). We also replicated the association signal of a coding SNP, CTLA4_+49_G/A (rs231775, P=0.0219). A common haplotype composed of CTLA4_-1722_T/C and CTLA4_(AT)n (an STRP marker: UniSTS:48500) showed protective effect (P=0.0004). Our results of family-based association study, taken together with those from the Caucasian population, provide evidence that CTLA4 confers susceptibility to GD across different ethnic backgrounds.
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
P-L
PL
Chen
C S-J
CS
Fann
C-C
CC
Chang
I-L
IL
Wu
W-Y
WY
Chiu
C-Y
CY
Lin
W-S
WS
Yang
T-C
TC
Chang
D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006111:Graves Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human