Dissertation
Dissertation > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Ankylosing spondylitis

Study on Relationship between HLA-B27, PDCD-1, IL-23R Gene Polymorphisms and Ankylosing Spondylitis

Author LiuXiang
Tutor HuLiHua
School Huazhong University of Science and Technology
Course Clinical Laboratory Science
Keywords Ankylosing Spondylitis HLA-B27 subtypes PCR-SSP PDCD-1 PCR-RFLP SNP IL-23R meta-analysis
CLC R593.23
Type PhD thesis
Year 2010
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Ankylosing spondylitis (Ankylosing Spondylitis, AS) is an immune complex disease, the combined effect of other genetic and environmental factors. Multiple studies have shown that genetic factors play a very important role in AS pathogenesis. The short arm of chromosome 6 of the human major histocompatibility meet the body (major histocompatibility complex, MHC) is the major genetic loci associated with AS. MHC Ⅰ encoding human leukocyte antigen B27 (human leukocyte antigen-B27, HLA-B27) is by far the strongest HLA antigens associated with the disease. The genome-wide scan found that in addition to the HLA-B27 gene, as well as other non-MHC genes involved in the pathogenesis of AS, AS belongs to autoimmune diseases areas, and immune-related genes associated with disease research, has become a study AS genetic one of the highlights in the background, such as interleukin (interleukin, IL) gene, procedures apoptosis (programmed cell death, PDCD) gene. Affected by a variety of factors, however, cause the results of these studies are not entirely consistent, especially single nucleotide polymorphisms (single nucleotide polymorphisms, SNP) and AS relations have not yet been fully clarified, pending further study. This topic by polymerase chain reaction - sequence specific primers (polymerase chain reaction-sequence-specific primer, PCR-SSP) method to study the correlation of the HLA-B27 gene isoforms in Hubei Province, China with AS first, and then apply the polymerase chain reaction - restriction fragment length polymorphism (polymerase chain reaction-restriction fragment length polymorphisms, PCR-RFLP) 3 SNP PDCD-1 gene was the AS disease association studies, and finally, the application of meta-analysis discussed Interleukin -23 receptor 10 (interleukin-23 receptor, IL-23R) gene SNP and AS correlation. The study is divided into the following three parts: Objective: To analyze the HLA-B27 gene isoforms with AS in Hubei Province in China to explore the role of the HLA-B27 gene isoforms in the pathogenesis of AS, as well as the evaluation of the HLA-B27 gene isoforms detected The clinical significance. Methods: HLA-B27 positive study collected a total of 346 cases. AS patients, 190 cases, male 129, female 61, average age (39 ± 9) years of age, and 156 healthy control subjects, male 81, female 75, mean age (30 ± 11) years of age. A case-control research program, the HLA-B27 gene isoforms detected by PCR-SSP. Results: 6 subtypes were detected, B * 2702, B * 2703, B * 2704, B * 2705, B * 2706 and B * 2713. AS patients and healthy control group, to B * 2704 subtype (72.1% and 56.4%) mainly followed by B * 2705 subtype (21.6% and 31.4%, respectively), the two groups were detected in the lower frequency B * 2702 subtypes (0.5% and 1.3%) and B * 2703 subtypes (5.3% and 8.3%, respectively), while the B * 2713 subtype in AS group only measured one cases (0.5%), B * 2706 Asian type measured in the healthy control group, only 4 patients (2.6%). AS patient group compared with the healthy control group, B * 2703 and B * 2705 subtypes in the higher frequency of the control group, but the difference between the two groups were not statistically significant (χ2 = 1.301, P gt; 0.05; χ2 = 4.032, P gt; 0.05), OR values ??and 95% confidence respectively for from 0.611 and 0.601,0.262-0.701 and 0.371-0.937. B * 2704 subtypes in the two groups in the proportion of all between the highest and the group there were significant differences (χ2 = 9.279, P lt; 0.01) OR value of 1.997,95% confidence interval 1.279-3.119, display B * 2704 subtype the AS incidence risk. Conclusion: The population of China's Hubei Province, B * 2704 and B * 2705 is a major subtypes, including B * 2704 was strongly correlated with AS, B * 2706 may be a negative correlation with the AS, other low frequency genetic subtypes with AS to be further explored, HLA-B27 gene isoforms can be used as important reference for the early diagnosis of AS. In addition, PCR-SSP method used in this study can detect 29 HLA-B27 subtypes (B * 2701-B * 2730, B * 2722 excluded), to meet the current needs of the HLA-B27 gene isoforms detected. Objective: To analyze the distribution of PDCD-1 gene SNP in AS patients and healthy control subjects, were compared differences in population distribution, to explore PDCD-1 gene polymorphism associated with susceptibility to AS, to the cause of the in-depth study of AS, the incidence The mechanism provides some theoretical basis. Methods: A case-control study program, blood samples were collected from 408 subjects, which includes 216 patients with AS specimens. 3 of PDCD-1 gene SNP loci (rs11568821, rs2227981, rs2227982) genotyping by PCR-RFLP technique χ2 test was used to compare the patient group and the control group genotype and allele frequency distribution differences, use SHESIS online software LD and gene analysis. Results: sites (rs11568821) in all AS patients and healthy control group, only found GG homozygous genotype was non-polymorphic; sites (rs2227981) in AS patients and healthy control group (CC) were zygote, CT heterozygotes and TT homozygotes three genotypes, but in both groups the locus genotype and allele frequency distribution of similar χ2 test was no significant difference (P = 0.145); sites (rs2227982) AS patients and healthy control group were detected in TT homozygotes, CT heterozygotes and CC homozygotes three genotypes, and the genotype and allele frequency in both groups with a significant difference (P = 0.025), the AS patients group the higher CT heterozygous genotype (P = 0.026, OR = 1.542,95% CI = 1.051-2.261), and T allele frequency (P = 0.004, OR = 1.553,95% CI = 1.144 -2.109). The use of the Online software of SHESIS analysis of rs2227981 and rs2227982 found that there existed a strong degree of chain (D '= 0.729); haplotypes constructed at the two sites, the the CT haplotype frequencies in AS patient group (21.6 %) than in the healthy control group (13.9%) (P = 0.002, OR = 1.712,95% CI = 1.222-2.397), CC haplotype in the healthy control group (57.1%) than patients with AS group (44.6%) more generally (P = 0.000, OR = 0.603,95% CI = 0.467-0.780). Conclusion: the Chinese Han population, the heterozygous rs2227982 in CT and T allele specific haplotype CT (PDCD-1.5/1.9) AS incidence was positively related to the CC haplotype AS incidence was negatively correlated, PDCD- The genetic correlation between gene polymorphism with AS. PDCD-1 gene polymorphisms with AS needed in more massive crowd research, in order to obtain more evidence for the purpose of: meta analysis of the domestic and foreign research results on IL-23R gene polymorphism with AS the relationship of the comprehensive evaluation of the IL-23R gene SNP with AS, AS population provide the basis for the assessment of the susceptibility genes. Methods: the electronic retrieval Medline database and the Chinese Journal Full-text database, according to certain criteria for quality assessment and data extraction, and the chi-square test of heterogeneity between the various studies, using Review Manager 4.2 software for statistical analysis. Results: A total of six studies met the inclusion criteria, study population involving nine categories, genotype frequency distribution all in compliance with the Hardy-Weinberg genetic equilibrium, the Egger test publication bias were not found. Meta-analysis, a total of 10 IL-23R SNP loci (rsll209026, rsl004819, rsl0489629, rsll465804, rsl34315, rsl0889677, rsl 1209032, rsl495965, rs7517847, rs2201841) allele test of homogeneity in addition to rs10889677 outside heterogeneity (P gt; 0.05), were not found, therefore rs10889677 using a random effects model, other sites using the fixed effects model to analyze the allele frequencies, comprehensive results showed that the alleles in all loci between the two groups distribution differences (P lt; 0.05), 5 sites (rsll209026, rsl0489629, rsll465804, rsl343151, rs7517847) allele in the control group distribution frequency is higher than the AS group, the other five sites and vice versa. Conclusion: IL-23R SNP with AS was positive or negative correlation, studied 10 alleles with AS was a negative correlation between the protective effect (patients) site: rs11209026 (G gt; A) rsl0489629 (G gt; A), rs11465804 (T gt; G), rsl343151 (C gt; T), rs7517847 (T gt; G). The remaining sites with AS were positively correlated. meta-analysis of the available higher statistical power, provide direction for further research and ideas.

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