ETS1基因变异使汉族人群易患强直性脊柱炎。

ETS1 variants confer susceptibility to ankylosing spondylitis in Han Chinese.

作者信息

Shan Shan, Dang Jie, Li Jiangxia, Yang Ze, Zhao Hailing, Xin Qian, Ma Xiaochun, Liu Yongchao, Bian Xianli, Gong Yaoqin, Liu Qiji

出版信息

Arthritis Res Ther. 2014 Apr 4;16(2):R87. doi: 10.1186/ar4530.

INTRODUCTION

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.

引言

ETS1是Th17分化基因的负调节因子，在自身免疫性疾病的发病机制中起核心作用。我们旨在研究ETS1基因多态性是否会使汉族人易患强直性脊柱炎（AS）。

方法

基于HapMap数据和先前的全基因组关联研究，我们在ETS1基因内选择了7个单核苷酸多态性（SNP）。基因分型采用TaqMan方法，对来自山东省的1015例AS患者和1132例健康对照，以及来自中国西北部宁夏地区的352例AS患者和400例健康对照进行检测。通过实时PCR测定基因表达。

结果

SNP rs1128334与AS显著相关（优势比1.204，95%置信区间1.06 - 1.37；P = 0.005）。这一关联在宁夏人群中得到证实（P = 0.015）。与对照组相比，rs12574073、rs1128334和rs4937333的单倍型TAT携带者患AS的风险增加，而单倍型CGC携带者风险降低。此外，AS患者中ETS1的表达低于对照组。rs1128334的风险等位基因A以及rs1128334和rs4937333的单倍型A - T与ETS1表达降低相关。