Wang Mengmeng, Xin Lihong, Cai Guoqi, Zhang Xu, Yang Xiao, Li Xiaona, Xia Qing, Wang Li, Xu Shengqian, Xu Jianhua, Shuai Zongwen, Ding Changhai, Pan Faming
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Department of Rheumatism and Immunity, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
PLoS One. 2017 May 11;12(5):e0177080. doi: 10.1371/journal.pone.0177080. eCollection 2017.
Previous studies have found the association between rs10865331 in 2p15 area and ankylosing spondylitis (AS). This study aimed to identify additional functional genetic variants in 2p15 region associated with AS susceptibility.
We used next generation sequencing (NGS) in 100 AS cases and 100 healthy controls to screen AS susceptible genetic variants, and validated these variants in 620 cases and 620 controls by using imLDRTM technique for single nucleotide polymorphism (SNP) genotyping.
Totally, we identified 12 SNPs that might confer susceptibility to AS. Of those SNPs, three (rs14170, rs2123111 and rs1729674) were nominally associated (P<0.05) with AS, but were no longer statistically significant after Bonferroni correction. After stratified by gender, another two SNPs (rs11428092 and rs10208769 in USP34) were associated with AS in males but not females, though this was not statistically significant after Bonferroni correction. In addition, rs1729674, rs14170, rs2123111 and rs10208769 were in strong linkage disequilibrium (LD) and were further enrolled in haplotype analysis. A novel haplotype TAGA was found to be associated with a decreased risk of AS (odds ratio (OR) (95% confidence interval (CI)) = 0.832 (0.705-0.982)). Beyond that, we also demonstrated a strong relationship between rs10865331 and AS susceptibility (OR (95% CI) = 1.303(1.111-1.526)).
rs14170 and rs2123111 inUSP34 and rs1729674 in C2orf74 may be associated with AS susceptibility in Han Chinese population. USP34 and C2orf74 in 2p15 region may be AS novel susceptibility genes.
既往研究发现2p15区域的rs10865331与强直性脊柱炎(AS)之间存在关联。本研究旨在鉴定2p15区域中与AS易感性相关的其他功能性遗传变异。
我们对100例AS患者和100例健康对照者进行了下一代测序(NGS)以筛选AS易感遗传变异,并通过使用imLDRTM技术进行单核苷酸多态性(SNP)基因分型,在620例患者和620例对照中验证了这些变异。
我们总共鉴定出12个可能赋予AS易感性的SNP。在这些SNP中,三个(rs14170、rs2123111和rs1729674)与AS呈名义上的关联(P<0.05),但在Bonferroni校正后不再具有统计学意义。按性别分层后,另外两个SNP(USP34中的rs11428092和rs10208769)与男性AS相关,但与女性无关,尽管在Bonferroni校正后这一结果无统计学意义。此外,rs1729674、rs14170、rs2123111和rs10208769处于强连锁不平衡(LD)状态,并进一步纳入单倍型分析。发现一种新的单倍型TAGA与AS风险降低相关(优势比(OR)(95%置信区间(CI))=0.832(0.705-0.982))。除此之外,我们还证明了rs10865331与AS易感性之间存在强关联(OR(95%CI)=1.303(1.111-1.526))。
USP34中的rs14170和rs2123111以及C2orf74中的rs1729674可能与中国汉族人群的AS易感性相关。2p15区域的USP34和C2orf74可能是AS新的易感基因。