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.
Chen
P-L
PL
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Fann
C S-J
CS
Chang
C-C
CC
Wu
I-L
IL
Chiu
W-Y
WY
Lin
C-Y
CY
Yang
W-S
WS
Chang
T-C
TC
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