Pathogenic variants screening in seventeen candidate genes on 2p15 for association with ankylosing spondylitis in a Han Chinese population

Mengmeng Wang; Lihong Xin; Guoqi Cai; Xu Zhang; Xiao Yang; Xiaona Li; Qing Xia; Li Wang; Shengqian Xu; Jianhua Xu; Zongwen Shuai; Changhai Ding; Faming Pan

doi:10.1371/journal.pone.0177080

Pathogenic variants screening in seventeen candidate genes on 2p15 for association with ankylosing spondylitis in a Han Chinese population

PLoS One. 2017 May 11;12(5):e0177080. doi: 10.1371/journal.pone.0177080. eCollection 2017.

Authors

Mengmeng Wang¹, Lihong Xin¹, Guoqi Cai¹, Xu Zhang¹, Xiao Yang¹, Xiaona Li¹, Qing Xia¹, Li Wang¹, Shengqian Xu², Jianhua Xu², Zongwen Shuai², Changhai Ding^{2

3}, Faming Pan^{1

3}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
² Department of Rheumatism and Immunity, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

Abstract

Objectives: 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.

Methods: 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.

Results: 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)).

Conclusions: 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.

MeSH terms

Asian People / genetics
China / epidemiology
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
High-Throughput Nucleotide Sequencing
Humans
Linkage Disequilibrium
Male
Membrane Proteins / genetics
Mitochondrial Proteins / genetics
Polymorphism, Single Nucleotide*
Spondylitis, Ankylosing / epidemiology
Spondylitis, Ankylosing / genetics*
Ubiquitin-Specific Proteases / genetics

Substances

CHCHD5 protein, human
Membrane Proteins
Mitochondrial Proteins
USP34 protein, human
Ubiquitin-Specific Proteases

Grants and funding

This study was supported by the grants from the National Natural Science Foundation of China (30771849, 30972530, 81273169 and 81573218). Faming Pan is supported by National Natural Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.