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

Abstract

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. 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. The frequency of A allele of rs171121187 was significantly higher in AS patients than in controls (Pc=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 (Pc=0.003, OR=3.96, 95% CI=1.80-8.75, and Pc=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 (Pc=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 (Pc=0.005, OR=0.46, 95% CI 0.18-1.14, and Pc=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). 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.