PTGER4基因多态性与山东汉族人群强直性脊柱炎易感性的关系

doi:10.6040/j.issn.1671-7554.0.2016.022

摘要/Abstract

摘要： 目的探讨PTGER4基因单核苷酸多态性(SNP)与山东汉族人群强直性脊柱炎(AS)的关系。方法利用TaqMan-PCR基因分型法对600例AS患者(AS组)和620例正常健康人(正常对照组)PTGER4基因SNPs位点rs7726237、rs4133101和rs16870224进行基因分型,计算各位点基因型和等位基因频率,比较两组各位点之间基因型和等位基因频率分布差异。结果 AS组与正常对照组PTGER4基因rs7726237位点A等位基因分布频率(78.5%, 74.7%)和G等位基因分布频率(21.5%,25.3%)的分布不同,差异有统计学意义(P=0.026, OR=0.81, 95%CI: 0.67~0.97);AS组GG、AG、AA基因型频率分布(5.3%、32.3%、62.3%)与对照组(5.2%、40.3%、54.5%)相比差异有统计学意义(P=0.014, OR=0.90, 95%CI: 0.54~1.51; P=0.014, OR=0.70, 95%CI: 0.55~0.89)。PTGER4基因rs4133101位点和rs16870224位点SNP在AS组和正常对照组差异均无统计学意义(P>0.05)。单倍体型分析与AS的易感性无关(P>0.05)。结论 PTGER4基因与山东汉族人群AS的易感性相关。

关键词: PTGER4, 脊柱炎, 多态性, 病例对照研究, 强直性

Abstract: Objective To investigate the relationship between the single nucleotide polymorphisms(SNPs)in PTGER4 and susceptibility of ankylosing spondylitis(AS)in the Han population in Shandong Province. Methods A total of 600 AS patients and 620 healthy controls were involved in this study. Three SNPs(rs7726237, rs4133101 and rs16870224)of PTGER4 gene were detected with the TaqMan-PCR method. The genotype and allele frequencies were calculated, and the distribution difference between the genotype and allele frequencies of SNPs was analyzed. Results Distribution frequencies of A alleles(78.5%, 74.7%)and G alleles(21.5%, 25.3%)of PTGER4 rs7726237 in AS and controls were significantly different with each other(P=0.026, OR=0.81, 95%CI: 0.67-0.97), while the distribution frequency of genotypes(GG, AG, AA)in group AS and controls were(5.3%, 32.3%, 62.3%)and(5.2%, 40.3%, 54.5%)(P=0.014, OR=0.90, 95%CI: 0.54-1.51 and P=0.014, OR=0.70, 95%CI: 0.55-0.89, respectively). Frequency of alleles and the genotypes of rs4133101 and rs16870224 SNPs between AS and controls group were similar(P>0.05). No association was found between haplotypes of SNPs in PTGER4 and susceptibility of AS(P>0.05). Conclusion This study indicates that PTGER4 gene polymorphism is related to AS susceptibility.

Key words: Case-control study, Polymorphism, PTGER4, Ankylosing spondylitis

中图分类号:

R593.24

王丽亚,麻贞贞,杨清锐. PTGER4基因多态性与山东汉族人群强直性脊柱炎易感性的关系[J]. 山东大学学报（医学版）, 2016, 54(6): 31-34.

WANG Liya, MA Zhenzhen, YANG Qingrui. Association between PTGER4 gene polymorphism and susceptibility of ankylosing spondylitis in Han population in Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 31-34.

参考文献

[1] Zambrano-Zaragoza JF, Agraz-Cibrian JM, Gonzalez-Reyes C, et al. Ankylosing spondylitis: from cells to genes[J]. Int J Inflam, 2013: 501653. doi: 10.1155/2013/501653.
[2] Van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial[J]. Arthritis Rheum, 2006, 54(7): 2136-2146.
[3] Braun J, Breban M, Maksymowych WP. Therapy for ankylosing spondylitis: new treatment modalities[J]. Best Pract Res Clin Rheumatol, 2002, 16(4): 631-651.
[4] Libioulle C, Louis E, Hansoul S, et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4[J]. PLoS Genet, 2007, 3(4): 58.
[5] Chun KS, Akunda JK, Langenbach R. Cyclooxygenase-2 inhibits UVB-induced apoptosis in mouse skin by activating the prostaglandin E2 receptors, EP2 and EP4[J]. Cancer Res, 2007, 67(5): 2015-2021.
[6] Nedelec E, Abid A, Cipolletta C, et al. Stimulation of cyclooxygenase-2-activity by nitric oxide-derived species in rat chondrocyte: lack of contribution to loss of cartilage anabolism[J]. Biochem Pharmacol, 2001, 61(8): 965-978.
[7] Burton PR, Clayton DG, Cardon LR, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants[J]. Nature Genetics, 2007, 39(11): 1329-1337.
[8] Mathies H. Diagnostic criteria in ankylosing spondylitis[J]. Dtsch Med Wochenschr, 1984, 109(10): 382-385.
[9] Rudwaleit M, van der Heijde D, Landewe R, et al. The development of Assessment of Spondylo Arthritis international Society classification criteria for axial spondylo arthritis(part II): validation and final selection[J]. Ann Rheum Dis, 2009, 68(6): 777-783.
[10] Rudwaleit M, Landewe R, van der Heijde D, et al. The development of Assessment of Spondylo Arthritis international Society classification criteria for axial spondylo arthritis(part I): classification of paper patients by expert opinion including uncertainty appraisal[J]. Ann Rheum Dis, 2009, 68(6): 770-776.
[11] 吴珊珊, 段振华, 潘发明. 强直性脊柱炎流行病学研究进展[J]. 安徽医科大学学报, 2013, 48(8): 988-992.
[12] Prijatelj M, Celhar T, Mlinaric-Rascan I. Prostaglandin EP4 receptor enhances BCR-induced apoptosis of immature B cells[J]. Prostaglandins Other Lipid Mediat, 2011, 95(1-4): 19-26.
[13] Yao C, Sakata D, Esaki Y, et al. Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion[J]. Nat Med, 2009, 15(6): 633-640.
[14] Glas J, Seiderer J, Czamara D, et al. PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohns disease and affect NF-kappaB and XBP1 binding sites[J]. PLoS One, 2012, 7(12): 52873. doi:10.1371/journal.pone.0052873.
[15] Perdigones N, Martin E, Robledo G, et al. Study of chromosomal region 5p13.1 in Crohns disease, ulcerative colitis, and rheumatoid arthritis[J]. Hum Immunol, 2010, 71(8): 826-828.
[16] Kabashima K, Saji T, Murata T, et al. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut[J]. J Clin Invest, 2002, 109(7): 883-893.
[17] Honda T, Segi-Nishida E, Miyachi Y, et al. Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis[J]. J Exp Med, 2006, 203(2): 325-335.
[18] Diamond JM, Akimova T, Kazi A, et al. Genetic variation in the prostaglandin E2 pathway is associated with primary graft dysfunction[J]. Am J Respir Crit Care Med, 2014, 189(5): 567-575.
[19] Chai W, Lian Z, Chen C, et al. JARID1A, JMY, and PTGER4 polymorphisms are related to ankylosing spondylitis in Chinese Han patients: a case-control study[J]. PLoS One, 2013, 8(9): 74794. doi:10.1371/journal.pone.0074794.
[20] Wang C, Liao Q, Hu Y, et al. T lymphocyte subset imbalances in patients contribute to ankylosing spondylitis[J]. Exp Ther Med, 2015, 9(1): 250-256.
[21] Gaston JS, Goodall JC, Baeten D. Interleukin-23: a central cytokine in the pathogenesis of spondylarthritis[J]. Arthritis Rheum, 2011, 63(12): 3668-3671.
[22] Niess JH, Brand S, Gu X, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance[J]. Science, 2005, 307(5707): 254-258.
[23] Wright PB, Mcentegart A, Mccarey D, et al. Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation[J]. Rheumatology(Oxford), 2016, 55(1): 120-132.
[24] Jethwa H, Bowness P. The interleukin(IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment[J]. Clin Exp Immunol, 2016, 183(1):30-36.
[25] 陈超, 李建军. IL-23/IL-17轴在强直性脊柱炎发病中的作用及治疗意义研究进展[J]. 天津医药, 2015, 43(10): 1213-1216. CHEN Chao, LI Jianjun. Roles of IL-23/IL-1 7 axis in pathogenesis and treatment of ankylosing spondylitis[J]. Tianjin Medical, 2015, 43(10): 1213-1216.

相关文章 15

[1]	葛丽娟金瑞峰王纪文许新升李癊. 多药耐药基因1 C1236T多态性与癫痫患者对药物反应性的相关性[J]. 山东大学学报(医学版), 2209, 47(6): 99-102.
[2]	孟朝暾,李钦, 孙卉,邬信芳,孙文凯,高伟. 白细胞介素18单核苷酸多态性与73例喉鳞状细胞癌易感性的关联性[J]. 山东大学学报 (医学版), 2020, 1(9): 58-63.
[3]	杜金阁,陈慧,杨孝荣,吕明. STAT4 rs7574865位点单核苷酸多态性与系统性红斑狼疮易感性Meta分析[J]. 山东大学学报（医学版）, 2017, 55(5): 95-102.
[4]	高萌,孙建民,蒋振松,崔新刚. MRI在布氏杆菌脊柱炎诊断中的应用价值[J]. 山东大学学报（医学版）, 2016, 54(6): 27-30.
[5]	木哈达斯·吐尔逊依明,帕它木·莫合买提,托兰古丽·买买提库尔班. CDKAL1(rs10946398 C/A)基因多态性与2型糖尿病易感性关系Meta分析[J]. 山东大学学报（医学版）, 2016, 54(2): 75-85.
[6]	陈思, 王牧川, 任楠楠, 许巍, 王玲玲, 栾海辉, 马俊, 刘艺鸣. Parkin基因多态性与山东省汉族帕金森病发病风险的关系[J]. 山东大学学报（医学版）, 2015, 53(4): 71-74.
[7]	张培艺, 周淑芬, 王梅英, 雷振华, 翁俊雄, 田野, 彭鑫, 傅碧玲, 邓柳霞, 邹世海, 郭成山. 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白抑制强直性脊柱炎趋化因子CXCL16及其受体CXCR6的表达[J]. 山东大学学报（医学版）, 2015, 53(12): 51-56.
[8]	唐习强, 梁烨, 李天资, 陈宏明, 李近都, 罗春英, 蓝家富. TNF-α-238G/A基因多态性与腹主动脉瘤的关联性[J]. 山东大学学报（医学版）, 2014, 52(S2): 5-6.
[9]	杨永荣, 李俊, 梁烨, 李近都, 蓝家富, 李天资. TNF-α-238G/A基因多态性与口腔扁平苔藓的关系[J]. 山东大学学报（医学版）, 2014, 52(S1): 10-11.
[10]	王尧, 陈艳红, 陈宏. 结肠癌患者外周血DPYD基因多态性与5-FU敏感性和毒副作用相关性分析[J]. 山东大学学报（医学版）, 2014, 52(S1): 18-21.
[11]	欧珠美朵, 嘎松卓嘎, 旦增. 白细胞介素-10基因多态性与西藏地区慢性乙型肝炎的相关性研究[J]. 山东大学学报（医学版）, 2014, 52(S1): 9-9.
[12]	王威严, 杨清锐, 袁苑, 杨杏林, 张源潮. 类风湿关节炎与TNFAIP3基因多态性关联研究的meta分析[J]. 山东大学学报（医学版）, 2014, 52(8): 75-80.
[13]	刘卫刚, 陆云, 李琳琳, 李筠青, 盛学文, 尹磊, 张功员, 赵景志. 河南省某地区人群肥胖易感性与神经肽Y及其受体基因多态性的关系[J]. 山东大学学报（医学版）, 2014, 52(8): 98-101.
[14]	王梅竹, 曹煜, 赵亮, 徐小珊, 张佩芳, 吕倩, 白逢彦, 康颖倩. 贵州地区临床酵母菌种类组成和分布[J]. 山东大学学报（医学版）, 2014, 52(8): 94-97.
[15]	侯丽君1，邢鹂健2，李广红1，刘燕3,亓文波4. 维生素D受体基因ApaI多态性与糖耐量减低的相关性[J]. 山东大学学报（医学版）, 2014, 52(6): 51-54.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed