Association Between SPARC Polymorphisms and Ankylosing Spondylitis and Its mRNA and Protein Expression in a Chinese Han Population: A Case-Control Study

Dongxia Liu; Liya Wang; Zhongdan Hu; Zhenzhen Ma; Qingrui Yang

doi:10.2147/IJGM.S419094

Association Between SPARC Polymorphisms and Ankylosing Spondylitis and Its mRNA and Protein Expression in a Chinese Han Population: A Case-Control Study

Int J Gen Med. 2023 Aug 16:16:3533-3542. doi: 10.2147/IJGM.S419094. eCollection 2023.

Authors

Dongxia Liu¹, Liya Wang^{1

2}, Zhongdan Hu³, Zhenzhen Ma¹, Qingrui Yang¹

Affiliations

¹ Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People's Republic of China.
² Department of Rheumatology and Immunology, Heze Medical College, Heze, 274000, People's Republic of China.
³ Tianjin Zhonghe Clinic Co. Ltd. of Heping District, Tianjin, 300450, People's Republic of China.

Abstract

Objective: We explore the association of polymorphisms in Secreted protein acidic and rich in cysteine (SPARC) with ankylosing spondylitis (AS) and detect SPARC mRNA and protein expression in a Chinese Han population.

Methods: Nine single-nucleotide polymorphisms (SNPs) of SPARC were genotyped in 768 AS patients and 768 controls by TaqMan genotyping assay. mRNA expression of SPARC was detected by real-time polymerase chain reaction (RT-PCR), and serum level of SPARC protein was detected by ELISA.

Results: The frequency of A allele of rs171121187 was significantly higher in AS patients than in controls (P_c=0.003, odds ratio [OR]=1.45, 95% confidence interval [95% CI] = 1.18-1.77), the AA and AC genotypes increased the risk of AS when compared with CC genotype (P_c=0.003, OR=3.96, 95% CI=1.80-8.75, and P_c=0.003, OR=1.27, 95% CI=1.01-1.61, respectively). The frequency of G allele of rs4958487 was significantly lower in AS than in controls (P_c=0.001, OR=0.60, 95% CI=0.47-0.68), the GG and GA genotypes reduced the risk of AS when compared with AA genotype (P_c=0.005, OR=0.46, 95% CI 0.18-1.14, and P_c=0.005, OR=0.60, 95% CI=0.45-0.79, respectively). The haplotype AA of rs17112187/rs4958487 significantly increased the risk of AS (P=2.31E-5, OR=1.60, 95% CI=1.28-1.98), while haplotype CG decreased the risk of AS (P=5.42E-5, OR=0.55, 95% CI=0.41-0.74). Expression levels of SPARC mRNA were significantly lower in both Peripheral blood mononuclear cells (PBMC) and granulocytes in AS patients than in controls (P=0.008 and P=0.005, respectively). SPARC protein levels were also reduced in AS patients versus the controls (P=0.002).

Conclusion: This study indicates that polymorphisms in SPARC are associated with AS susceptibility, and both mRNA and protein levels of SPARC are decreased in AS patients in a Chinese Han population.

Keywords: SNP; SPARC; ankylosing spondylitis; case–control study; secreted protein acidic and rich in cysteine; single nucleotide polymorphism.

Grants and funding

This work was supported by Natural Science Foundation of China Grant [No. 81172861/H1008 and No. 81671605/H1008], Foundation of Scientific and Technological Project of Shandong Province [No. 2011GG21829], Shandong Province Excellent Middle-aged and Young Scientists Encouragement Research Foundation [No. BS2009YY025], and the National Natural Science Foundation of China (Youth fund project, Grant No. 82201994).