Background Ankylosing spondylitis (AS) is a highly heritable complex inflammatory arthritis disease. Genetic factors are thought to be crucial in the pathogenesis of ankylosing spondylitis. However, few studies were performed to investigate the relationship between HLA-DP/DQ and STAT4 polymorphisms and AS susceptibility.
Objectives To further explore the associations of the four SNPs (HLA-DP rs3077, HLA-DP rs9277535, HLA-DQ rs7453920 and STAT4 rs7574865) with the risk and clinical characteristics of AS in a Chinese Han population. And also to analyze the linkage disequilibrium (LD) in HLA gene and the association between the HLA haplotypes and the susceptibility to AS.
Methods 400 patients with AS and 379 age- and sex-matched healthy controls in a Chinese population were included. All the four SNPs were genotyped using polymerase chain reaction high resolution melting (HRM) analysis. Allele, genotype, and haplotype frequencies were compared between AS patients and controls. Besides, stratification analyses of HLA-DP/DQ and STAT4 polymorphisms and risk for AS were also performed.
Results No significant difference was observed between AS patients and healthy controls in the allele frequency of rs3077, rs9277535 and rs7574865. However, there was a significant association between the HLA-DQ rs7453920 G/A variant and AS patients, with minor allele A correlated with a reduced risk of AS (allelic frequency, OR=0.44, 95% CI: 0.31–0.62, p=3.0E-06; dominant model, OR =0.42, 95% CI: 0.29–0.62, p=7.0E-06). Moreover, the haplotypes block AAA and GGA in the HLA gene significantly correlated with reduced risk of AS (AAA: OR =0.38, 95%CI: 0.22–0.66, p=0.0004; GGA: OR=0.41, 95% CI: 0.24–0.69, p=0.0006).
Conclusions This is the first study demonstrating the relationship between HLA-DQB2 rs7453920 and the risk of AS in a Chinese population. Besides, this study revealed that LD blocks around HLA–DP/DQ are strongly associated with AS susceptibility. This research sheds new light on the significant relationship between the SNPs in the HLA gene and the risk of AS.
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Acknowledgement This study was supported by the National Natural Science Foundation of China (No. 81301496, 81202354).
Disclosure of Interest X. Liu Shareholder of: No, Grant/research support from: National Natural Science Foundation of China (No. 81301496), Consultant for: No, Employee of: No, Paid instructor for: No, Speakers bureau: No, L. Wang Shareholder of: No, Grant/research support from: National Natural Science Foundation of China (No. 81301496), Consultant for: No, Employee of: No, Paid instructor for: No, Speakers bureau: No, B. Yang Shareholder of: No, Grant/research support from: National Natural Science Foundation of China (No. 81301496), Consultant for: No, Employee of: No, Paid instructor for: No, Speakers bureau: No