ETS1 variants confer susceptibility to ankylosing spondylitis in Han Chinese.
BACKGROUND
ETS1 is a negative regulator of the Th17 differentiation gene and plays a central role in the pathogenesis of autoimmune diseases. We aimed to investigate whether polymorphisms in ETS1 confer susceptibility to ankylosing spondylitis (AS) in Han Chinese.


METHODS
We selected seven single nucleotide polymorphisms (SNPs) within ETS1 based on HapMap data and previous genome-wide association study. Genotyping involved the TaqMan method in 1,015 patients with AS and 1,132 healthy controls from Shandong Province, and 352 AS patients and 400 healthy controls from Ningxia, a northwest region in China. Gene expression was determined by real-time PCR.


RESULTS
The SNP rs1128334 was strongly associated with AS (odds ratio 1.204, 95% confidence interval 1.06-1.37; P = 0.005). This association was confiexrmed in the Ningxia population (P = 0.015). Carriers of the haplotype TAT for rs12574073, rs1128334 and rs4937333 were associated with increased risk of AS and haplotype CGC with reduced risk as compared to controls. In addition, ETS1 expression was lower in AS patients than controls. The risk allele A of rs1128334 and haplotype A-T of rs1128334 and rs4937333 were associated with decreased expression of ETS1.


CONCLUSIONS
Common variants in ETS1 may contribute to AS susceptibility in Han Chinese people.
Shan
S
Shan
Jie
J
Dang
Jiangxia
J
Li
Ze
Z
Yang
Hailing
H
Zhao
Qian
Q
Xin
Xiaochun
X
Ma
Yongchao
Y
Liu
Xianli
X
Bian
Yaoqin
Y
Gong
Qiji
Q
Liu
D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000235:genetics*
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1