Study On Relationship Between HLA-B27, PDCD-1, IL-23R Gene Polymorphisms And Ankylosing Spondylitis

Ankylosing Spondylitis (AS) is an immune-related complex disease caused by a combination of genetic and environmental factors. A lot of studies show that genetic factors play an important role in the development of AS.The MHC (major histocompatibility complex) on chromosome 6p is strongly linked and associated with AS. The association of HLA-B27 (human leukocyte antigen-B27) coded by MHCⅠwith AS is the strongest among genetic association with other disease. Genome-wide screening studies have led to the identification of several non-MHC genes possibly linked to AS. Due to autoimmune mechanisms participating in the pathogeneisis of AS, studies on the disease association with certain genes involved in the autoimmune response may highlight the genetic background of AS, such as the genes IL (interleukin), PDCD (programmed cell death) and et al. However, the results are not unified and repeated because of many reasons, especially relation between SNPs (single nucleotide polymorphisms) and AS. Therefore, a more thorough search for polymorphisms in the locus will be needed.In this study, we firstly investigated the the association of the B27 subtypes with AS in the HuBei population of China by PCR-SSP (polymerase chain reaction-sequence-specific primer). Then, by employing PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphisms), we analyzed the association of PDCD-1 (programmed cell death) SNP and haplotypes with AS. At last, a meta-analysis was conducted to determine the contribution of IL-23R (interleukin-23 receptor) gene SNP previously implicated in AS susceptibility. The present study can be divided into the following three parts. OBJECTIVE To analyze the association of the B27 subtypes with AS in the HuBei population of China, investigate the role of B27 subtypes in the etiology of AS, and evaluate the usefulness of HLA-B27 subtype in clinical diagnosis of AS.METHODS A total of 190 patients with AS and a control group of 156 subjects were recruited for the study. Of 190 AS patients,129 were men and 61 women, with a mean age of 39±9. HLA-B27 subtypes were confirmed by PCR-SSP.RESULTS Six B27 subtypes were determined:B*2702,03,04,05,06 and B*13. HLA-B*2704 (patients 72.1% vs. controls 56.4%) and HLA-B*2705 (patients 21.6% vs. controls 31.4%) were the two high frequency genotypes in controls and patients. There were significant differences in the distribution of B*2704 subtypes between patients with AS and controls (χ2=9.279, P<0.01, OR=1.997,95% CI=1.279-3.119). Compared with the controls, the AS patients had high frequency of B*2704 and low frequency of B*2705. B*2703 was detected in 10 (5.3%) patients and in 13 (8.3%) controls. B*2702, B*2706 and B*2713 were relatively rare. Other HLA-B27 subtypes were relatively rare. One B*2713 was solely detected in AS group but not in controls, four B*2706 were found only in controls.CONCLUSION B*2704 was the dominant subtypes followed by B*2705. B*2704 is strongly associatied with AS. B*2706 may have a negative association with AS. Subtyping for HLA-B27 by PCR-SSP has been proved to be suitable for clinical application. It is useful to diagnose AS in clinic. OBJECTIVE To investigate the association of PDCD-1 polymorphisms and haplotypes with AS in Chinese Han population.METHODS In a case-control association study, three SNP, PDCD-1.3 G/A, PDCD-1.5 C/T and PDCD-1.9 T/C, were genotyped in 216 AS patients and 264 healthy controls using PCR-RFLP assay.RESULTS All genotype distributions in the patients and in the controls were in Hardy-Weinberg equilibrium. The associations of genotypes and alleles with AS were analyzed. The genotype distributions of PDCD-1.9 were significantly different between the patients with AS and the controls (P=0.025). The frequencies of TC genotype and T allele of PDCD-1.9 were higher in the patients than those in the controls (P=0.026 and 0.004). No association for PDCD-1.5 in AS was found, and PDCD-1.3 was nonpolymorphic in Chinese Han population. Moreover, significant LD was found between PDCD-1.5 and PDCD-1.9 (D'=0.729). Four haplotypes between SNPs PDCD-1.5 and PDCD-1.9 were constructed. The frequency of the CT haplotype was higher in the AS patients (21.6%) than the controls (13.9%) (P=0.002, OR=1.712,95%CI=1.222-2.397). The CC haplotype was more common in controls (57.1%) than in patients (44.6%) (P=0.000, OR=0.603,95% CI=0.467-0.780).CONCLUSION The results support a genetic association between the PDCD-1 polymorphism and susceptibility to AS in Chinese Han population. A more thorough search in other populations will be needed. OBJECTIVE To determine the contribution of IL-23R gene SNP previously implicated in AS susceptibility in different populations worldwide.METHODS An electric search was performed in PubMed and Chinese periodical full-text database. Association between IL-R23 SNP and AS was examined. Data on allele frequency was extracted. Heterogeneity, power and publication bias were explored. Odds ratio Was summarized. All were perfermed by Review Manager 4.2 software.RESULTS Six studies of IL-R23 SNP were enrolled. The alleles frequency of 10 SNP (rs11209026, rs1004819, rs10489629, rs11465804, rs134315,rs10889677, rs11209032,rs1495965, rs7517847, rs2201841) were analyzed in AS cases and controls recruited in 9 different centres. No heterogeneity and publication bias were observed (P>0.05) except rs10889677. Thus, random effect mode (DerSimonian-Laird test) was used to calculate OR of rs10889677, fixed effect mode (Peto test) was used in others SNPs. All allele distributions were significantly different between the patients with AS and the controls (P<0.05). The alleles frequency of 5 SNP (rs11209026, rs10489629, rs11465804, rs1343151, rs7517847) was higher in the controls than in AS patients.CONCLUSION This study confirms that IL-23R SNP is associated with susceptibility to AS. Meta-analysis is a useful tool by providing sufficiently large sample sizes to produce robust findings.