Association Study Between Human FCRL Family Genes Single Nucleotide Polymorphism With AS In Chinese Han Population

Ankylosing spondylitis (Ankylosing Spondylitis, AS) is a seronegative, chronic inflammatory autoimmune disease, which mainly affects the axial skeleton of the young men with a higher clinical incidence and family aggregation. The exact cause of the disease is currently unknown, it is generally accepted that AS is a very complex disease, also known as a multi-factorial diseases. Although many previous studies aimed at the etiology and pathogenesis of AS has been put forward many theories, including molecular simulation theory, theory of peptide-induced arthritis, HLA-B27 molecules of non-folded protein hypothesis, etc.But so far, the exact cause of AS remains unclear. However, a large number of domestic and overseas studies have shown that genetic factors take an important part in the pathogenesis of AS, a genome-wide scan have revealed multiple regions associated with AS susceptibility [1,2]. Among them, HLA region, represented by HLA-B27 gene, have robust association with AS, studies on HLA-B27 and the genetic susceptibility to AS has gone through more than 30 years, which have been confirmed in different countries and regions, but the exact pathogenesis of AS is still not very clear, and the entire HLA region can explain only a fraction (40 -50%) of AS genetic susceptibility, therefore, the non-HLA genes may also be associated with the susceptibility to AS.The purpose of this study was to explore the association of single nucleotide polymorphisms (SNPs) and haplotypes of Fc receptor-like genes with susceptibility to AS in a Chinese Han population, and to explore the interaction of genes and the environmental factors.Questionnaire investigation was performed to obtain information in this case-control study. we collected 169 cases of HLA-B27 positive AS patients (107 males and 62 females) from the department of rheumatology, the first affiliated hospital of Anhui Medical University, including outpatient and inpatient. 184 HLA-B27 positive healthy controls (112 male and 72 female) are also recruited from the same region. Their general epidemiological data and DNA samples were collected. in this study, we have chosen an important candidate family gene (immunoglobulin receptor homologue family gene) for AS . 9 non-synonymous mutation functional SNPs, from FCRL1 (1 SNP), FCRL3 (3 SNPs), FCRL4 (1 SNP) and FCRL5 (4 SNPs) respectively, are genotyped by PCR ligase detection reaction method to obtain their genotype frequency and haplotype in population. The database was established by EPIdata 3.0 software. The Social Science Statistical Package (SPSS10.01) and the classic case-control on-line analysis Software Shesis (http://analysis.bio-x.cn/myAnalysis.php) are used for statistical analysis.In total,169 patients are recruited, with an average age of 26.38±6.32 years, ranging form 14 to 78 years. through multiple SNP loci screening, except for FCRL5, FCRL1, FCRL3 and FCRL4 gene was not associated with AS genetic susceptibility.2 SNPs(rs12036228 and rs6427384) from FCRL5 gene is associated with AS. C allele in rs12036228 occurred more frequently in case group than in control group,and T allele in rs6427384 more frequently in case group. haplotype C-T, On the basis of the two SNPs above, occurres more frequently in case group than in control group,but haplotype C-C more frequently in control. Meanwhile, we analyzed the HLA-B27 gene subtypes and find that there are four subtypes (B * 2703,B * 2704, B * 2705 and B * 2706) in the Chinese Han population, in which B * 2704 and B * 2705 frequence in case group are more common than the others, accounting for 53.8% and 34.9% and the two subtypes is also more common in control group. The difference of HLA-B27 gene subtype frequence is not statistically significant between case group and control group ( 2=7.014, P = 0.056). In the study we find that environmental risk factors is not associated with the general back pain level in patients with AS. the results of multivariate analysis shows that Such factors as gender, disease duration, education, drinking history may be associated with the BASDFI of patients with AS. Meanwhile, the environmental factors and two SNPs associated with AS above is analyzed by non-conditional logistic regression analysis on the basis of other independent variables adjusted. the results showed that the two variables(infection history and family living environment) go into the model, but no interactions of FCRL5 gene with environmental factors was found associated with AS.In summary, our results suggested that FCRL family genes (located on 1q21-23 region), in particular FCRL5 gene, may be related to the genetic susceptibility to AS in the Chinese Han population. In addition, environmental factors also paly an important role in the onset of AS. However, no interactions of FCRL genes with environmental factors was found. Nevertheless, the sample size is relatively small, further studies in different populations are still needed.