| BackgroundAnkylosing spondylitis (AS) is a chronic progressive autoimmune disease which involves the joints of axial skeletons and attachment points of tendons and ligaments at bones, with its rheumatoid factor negative. It is a polygenic disease which is influenced by both hereditary and environmental factors. But the exact etiology and pathogenesis of AS is still not clear.The significant feature of AS is to be strongly associated with the HLA-B27, and the genetic risk factors account for about 16% in all. This suggests that there are other genes relevant with AS. In recent years, genome-wide scan analysis confirmed that there were other sites of predisposing genes in both inside and outside the HLA gene region. Endoplasmic reticulum aminopeptidase (ERAP) is involved in the regulation of number and concentrations among cytokines, cytokine membrane receptors and soluble receptors, while this process plays a key role in the pathogenesis of AS. In 2007, whole-genome association analysis made in the populations of Europe, America and Oceania prompted:ERAP1 gene may be a new susceptibility gene of AS outside the HLA-B27. Toll-like receptor (TLR) serves as a bridge between natural immunity and acquired immunity. Sacroiliitis is a characteristic mark of AS, while there were studies show that TLR9 played a role in arthritis. The superfamily of transforming growth factorβ(TGFβ) regulate in many processes such as cell growth, differentiation, apoptosis and immune response. Some scholars believe that, hip and knee joint get inflamed in early stage of AS, and then gradually develop into rigidity, this process may be related to TGFβ1. However, there is no report that has shown the relationship between such candidate genes and AS in Chinese Han population till now.ObjectiveTo investigate the association of single nucleotide polymorphism site rs27044 of ERAP1 gene, site rs55704465 of TLR9 gene and site rs1800470 of TGFβ1 gene with ankylosing spondylitis. Then provide a theoretical basis to further study in the pathogenesis of AS.MethodsThe 191 sporadic cases of AS made final diagnosis at departments of rheumatology and orthopedic were collected from March to August 2009. All patients' diagnosis accord with the evaluation of diagnostic criteria for ankylosing spondylitis made at 1984 in New York.209 cases of healthy adults were selected as controls. Collect the blood samples of both groups and extract genomic DNA. Detect the polymorphisms of the three sites by polymerase main reaction and restriction fragment length polymorphism (PCR-RFLP). Determine the individual genotypes according to the results of agarose gel electrophoresis. Use SPSS 13.0 statistical package for the chi-square test (χ2) analysis. Analyze the genotype distribution according to Hardy-Weinberg equilibrium(HWE). Calculate the allele, genotype odds ratio (OR).Results(1)In the genotype analysis of rs27044 site in ERAP1 gene, the frequencies of genotypes GG, GC, CC in AS group were 0.126,0.408 and 0.466, while 0.455,0.402, 0.143 in control group, respectively. The difference between the two groups was statistically significant(χ2=71.170,P＜0.05). The frequencies ratios for allele G and C in AS group were 0.330 and 0.670, while 0.656 and 0.344 in control group, respectively. The difference between the two groups was statistically significant (χ 2=21.215, P＜0.05)(2) In the genotype analysis of rs55704465 site in TLR9 gene, the frequencies of genotypes CC, TC, TT in AS group were 0.194,0.424 and 0.382, while 0.230,0.440, 0.330 in control group, respectively. No statistically significance was observed between the two groups(χ2=1.429,P＞0.05). The frequencies ratios for allele C and T in AS group were 0.406 and 0.594, while 0.450 and 0.550 in control group, respectively. No statistically significance was observed between the two groups (χ2=0.395, P＞0.05)(3) In the genotype analysis of rs 1800470 site in TGFβ1 gene, the frequencies of genotypes AA, AG, GG in AS group were 0.283,0.466 and 0.251, while 0.234, 0.469,0.297 in control group, respectively. No statistically significance was observed between the two groups(χ2=1.651,P＞0.05). The frequencies ratios for allele C and T in AS group were 0.516 and 0.484, while 0.469 and 0.531 in control group, respectively. No statistically significance was observed between the two groups (χ2=0.438, P＞0.05)Conclusions(1)The polymorphism of rs27044 site in ERAP1 gene is associated with AS in Shandong Han population.(2)The polymorphism of rs55704465 site in TLR9 gene is not associated with AS in Shandong Han population(3)The polymorphism of rs1800470 site in TGFβ1 gene is not associated with AS in Shandong Han population.
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