Aiolos基因多态性与贵州汉族人群系统性红斑狼疮的相关性
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摘要
目的探讨贵州汉族人群Aiolos基因rs9909593、rs9635726、rs12150079位点多态性与系统性红斑狼疮(SLE)的相关性。方法采用病例对照研究,利用SNaPshot技术对贵州汉族213例SLE患者(SLE组)和187例健康对照组的Aiolos基因3个SNP位点rs9909593、rs9635726及rs12150079进行分型,比较两组间基因型频率及等位基因频率的差异,利用非条件logistic回归模型分析基因与疾病易感性的关系。结果 Aiolos rs9909593位点AG、GG、AA基因型频率和等位基因A、G频率在贵州汉族SLE组和健康对照组分别为0.437%、0.080%、0.483%和0.412%、0.064%、0.524%;0.702%、0.298和0.730%、0.270%,两组间基因型频率和等位基因频率分布差异均无统计学意义(P>0.05);Aiolos rs9635726位点CT、CC、TT基因型频率和等位基因C、T频率在贵州汉族SLE组和健康对照组分别为0.437%、0.094%、0.469%和0.422%、0.064%、0.513%;0.312%、0.688%和0.275%、0.725%,两组间基因型频率和等位基因频率分布差异均无统计学意义(P>0.05);Aiolos rs12150079位点AG、GG、AA基因型频率和等位基因A、G频率在贵州汉族SLE组和健康对照组分别为0.310%、0.042%、0.648%和0.326%、0.032%、 0.642%;0.197%、0.803%和0.195%、0.805%,两组间基因型频率和等位基因频率分布差异均无统计学意义(P>0.05)。非条件logistic回归模型分析提示rs9909593、rs9635726及rs12150079位点在加性模型、显性模型及隐性模型下均与SLE无相关(P>0.05)。这3个SNP间rs12150079与rs9635726、rs9909593存在完全连锁不平衡(D′≥1,r~2≥0.584);rs9635726与rs9909593存在强连锁不平衡(D′=0.877,r~2=0.733)。联合基因型分析发现,5种单体型(ACG、GCA、GCG、GTA、GTG)在SLE组及健康对照组中的分布差异无统计学意义(P>0.05),同时非条件logistic回归分析显示,各单体型与SLE发病均无关。结论 Aiolos基因rs9909593、rs9635726及rs12150079单核苷酸多态性可能与贵州汉族人群SLE的患病风险无相关性。
Objective To investigate the correlations of the polymorphism of Aiolos gene rs9909593, rs9635726 and rs12150079 with systemic lupus erythematosus(SLE) in Guizhou Han population. Methods The case-control study was conducted on 213 SLE patients and 187 healthy controls. The 3 SNPs(rs9909593, rs9635726 and rs12150079) of Aiolos gene was analyzed by snapshot technology. The susceptibility between gene and SLE was analyzed through the non-conditional logistic-regression model. Results The frequencies of genotype AG, GG and AA in SLE group were 0.437%, 0.080% and 0.483%, respectively; and in control group were 0.412%, 0.064% and 0.524%, respectively. The frequencies of allele A and G of Aiolos rs9909593 were 0.702% and 0.298%, respectively, in SLE group; and 0.730% and 0.270%, respectively, in control group. There was no significant difference in genotype frequency or allele frequency of Aiolos rs9909593 between the two groups(P>0.05). The frequencies of genotype CT, CC and TT in SLE group were 0.437%, 0.094% and 0.469%, respectively; and in control group were 0.422%, 0.064% and 0.513%, respectively. The frequencies of C and T in SLE group were 0.312% and 0.688%, respectively;and in control group were 0.275% and 0.725 %, respectively. There was no significant difference in genotype frequency and allele frequency of Aiolos rs9635726 between the two groups(P>0.05). The frequencies of genotype AG, GG and AA of Aiolos rs12150079 in SLE group were 0.310%, 0.042% and 0.648%, respectively; and in control group were 0.326%, 0.032% and 0.642%, respectively. The frequencies of allele A and G of Aiolos rs12150079 in SLE group were 0.197% and 0.803%, respectively; and in control group were 0.195% and 0.805%, respectively. There was no significant difference in genotype frequency or allele frequency of Aiolos rs12150079 between the two groups(P>0.05). Logistic regression model analysis suggested that rs9909593, rs9635726 and rs12150079 had no significant correlation with SLE in the additive model, dominant model and implicit model(P>0.05). The rs12150079 were completely unbalant with rs9635726 and rs9909593(D′≥1, r~2≥0.584). The rs9635726 and rs9909593 had strong linkage disequilibrium(D′=0.877, r~2=0.733). Joint genotype analysis found that there was no significant difference in the distribution of 5 single haplotype(ACG, GCA, GCG, GTA, GTG) between SLE group and control group(P>0.05). The non-conditional logistic-regression model analysis showed that the haplotype had nothing to do with the incidence of SLE. Conclusion The single nucleotide polymorphism of Aiolos gene rs9909593, rs9635726 and rs12150079 is not associated with the risk of SLE in Guizhou Han population.
Objective To investigate the correlations of the polymorphism of Aiolos gene rs9909593, rs9635726 and rs12150079 with systemic lupus erythematosus(SLE) in Guizhou Han population. Methods The case-control study was conducted on 213 SLE patients and 187 healthy controls. The 3 SNPs(rs9909593, rs9635726 and rs12150079) of Aiolos gene was analyzed by snapshot technology. The susceptibility between gene and SLE was analyzed through the non-conditional logistic-regression model. Results The frequencies of genotype AG, GG and AA in SLE group were 0.437%, 0.080% and 0.483%, respectively; and in control group were 0.412%, 0.064% and 0.524%, respectively. The frequencies of allele A and G of Aiolos rs9909593 were 0.702% and 0.298%, respectively, in SLE group; and 0.730% and 0.270%, respectively, in control group. There was no significant difference in genotype frequency or allele frequency of Aiolos rs9909593 between the two groups(P>0.05). The frequencies of genotype CT, CC and TT in SLE group were 0.437%, 0.094% and 0.469%, respectively; and in control group were 0.422%, 0.064% and 0.513%, respectively. The frequencies of C and T in SLE group were 0.312% and 0.688%, respectively;and in control group were 0.275% and 0.725 %, respectively. There was no significant difference in genotype frequency and allele frequency of Aiolos rs9635726 between the two groups(P>0.05). The frequencies of genotype AG, GG and AA of Aiolos rs12150079 in SLE group were 0.310%, 0.042% and 0.648%, respectively; and in control group were 0.326%, 0.032% and 0.642%, respectively. The frequencies of allele A and G of Aiolos rs12150079 in SLE group were 0.197% and 0.803%, respectively; and in control group were 0.195% and 0.805%, respectively. There was no significant difference in genotype frequency or allele frequency of Aiolos rs12150079 between the two groups(P>0.05). Logistic regression model analysis suggested that rs9909593, rs9635726 and rs12150079 had no significant correlation with SLE in the additive model, dominant model and implicit model(P>0.05). The rs12150079 were completely unbalant with rs9635726 and rs9909593(D′≥1, r~2≥0.584). The rs9635726 and rs9909593 had strong linkage disequilibrium(D′=0.877, r~2=0.733). Joint genotype analysis found that there was no significant difference in the distribution of 5 single haplotype(ACG, GCA, GCG, GTA, GTG) between SLE group and control group(P>0.05). The non-conditional logistic-regression model analysis showed that the haplotype had nothing to do with the incidence of SLE. Conclusion The single nucleotide polymorphism of Aiolos gene rs9909593, rs9635726 and rs12150079 is not associated with the risk of SLE in Guizhou Han population.
引文
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[11] Cantor RM,Yuan J,Napier S, et al.Systemic lupus erythematosus genome scan:support for linkage at 1q23,2q33,16q12-13,and 17q2l-23 and novel evidence at 3p24,10q23-24,13q32,and 18q22-23[J].Arthritis Rheum,2004,50(10):3203-3210.
[12] Cunninghame Graham DS, Morris DL,Bhangale TR, et al.Association of NCF2,IKZF1, IRF8,IFIH1, and TYK2 with systemic lupus erythematosus[J].PLoS Genet,2011,7(10):e1002341.
[13] You Y, Zhai ZF, Chen FR,et al.Autoimmune risk loci of IL12RB2, IKZF1, XKR6,TMEM39A and CSK in Chinese patients with systemic lupus erythematosus[J].Tissue Antigens,2015,85(3):200-203.
[14] Zhang YM, Zhou XJ,Cheng FJ,et al.Association of the IKZF1 5′ UTR variant rs1456896 with lupus nephritis in a northern Han Chinese population[J].Scand J Rheumatol,2017,46(3):210-214.
[15] Wang C, Ahlford A, J?rvinen TM, et al.Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations[J].Eur J Hum Genet,2013,21(9):994-999.
[16] 杨莹,陈晓红,刘样满.等. SLE患者外周血单个核细胞中Aiolos mRNA的表达[J].中国皮肤性病学杂志,2013,27(4):331-336.
[17] 刘样满,陈晓红,杨莹.等.转录因子Aiolos基因在系统性红斑狼疮中的表达[J].中华皮肤病学杂志,2010,43(7):471-473.
[18] Lessard CJ, Adrianto I, Ice JA, et al.Identification of IRF8,TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study[J].Am J Hum Genet,2012,90(4):648-660.
[19] 叶丽霞,付朝伟,江峰,等.锌指蛋白基因IKZF3多态性与中国长江以南汉族人群系统性红斑狼疮的病例对照研究[J].中华流行病学杂志,2016,37(7):996-1002.
[20] Cai X,Qiao Y,Diao C,et al. Association between polymorphisms of the IKZF3 gene and systemic lupus erythematosus in a Chinese Han population[J].PLoS One,2014,9(10):e108661.
[2] 刘世林,廖艳霞,董光富. 系统性红斑狼疮患者外周血B细胞脂笩表达变化及地塞米松对其的影响[J]. 广东医学,2018,39(12):1815-1818.
[3] 曾丽华,岳锐,龙欣欣,等. 系统性红斑狼疮患者外周血IL-17+T淋巴细胞的表达及其与疾病活动性的关系[J]. 广东医学,2018,39(7):1008-1012.
[4] 张继云,李文艳,赵旌,等. 系统性红斑狼疮患者维生素D与T淋巴细胞亚群及α 干扰素的相关性[J]. 广东医学,2017,38(8):1192-1194.
[5] Qiu R,Zhang H,Zhao H,et al.Genetic variants on 17q21 are associated with ankylosing spondylitis susceptibility and severity in a Chinese Han population[J].Scand J Rheumatol,2013,42(6):469-472.
[6] Kurreeman FA,Stahl EA,Okada Y,et al.Use of a multiethnic approach to identify rheumatoid-arthritis-susceptibility loci,lp36and 17q12[J].Am J Hum Genet,2012,90(3):524-532.
[7] Marinho S,Custovic A,Marsden P,et al.17q12-21 variants are associated with asthma and interact with active smoking in an adult population from the United Kingdom[J].Ann Allergy Asthma Immunol,2012,108(6):402-411.e9.
[8] Lessard CJ,Adrianto I,Ice JA,et al.Identification of 1RF8.TMEM39A,and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study[J].Am J Hum Genet,2012,90(4):648-660.
[9] Hochberg MC,Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J].Arthritis Rheum,1997,40(9):1725.
[10] Hosokawa Y,Maeda Y,Takahashi EI,et al.Human aiolos,an ikaros-related zinc finger DNA binding protein:cDNA cloning,tissue expression pattern,and chromosomal mapping[J].Genomics,1999,61(3):326-329.
[11] Cantor RM,Yuan J,Napier S, et al.Systemic lupus erythematosus genome scan:support for linkage at 1q23,2q33,16q12-13,and 17q2l-23 and novel evidence at 3p24,10q23-24,13q32,and 18q22-23[J].Arthritis Rheum,2004,50(10):3203-3210.
[12] Cunninghame Graham DS, Morris DL,Bhangale TR, et al.Association of NCF2,IKZF1, IRF8,IFIH1, and TYK2 with systemic lupus erythematosus[J].PLoS Genet,2011,7(10):e1002341.
[13] You Y, Zhai ZF, Chen FR,et al.Autoimmune risk loci of IL12RB2, IKZF1, XKR6,TMEM39A and CSK in Chinese patients with systemic lupus erythematosus[J].Tissue Antigens,2015,85(3):200-203.
[14] Zhang YM, Zhou XJ,Cheng FJ,et al.Association of the IKZF1 5′ UTR variant rs1456896 with lupus nephritis in a northern Han Chinese population[J].Scand J Rheumatol,2017,46(3):210-214.
[15] Wang C, Ahlford A, J?rvinen TM, et al.Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations[J].Eur J Hum Genet,2013,21(9):994-999.
[16] 杨莹,陈晓红,刘样满.等. SLE患者外周血单个核细胞中Aiolos mRNA的表达[J].中国皮肤性病学杂志,2013,27(4):331-336.
[17] 刘样满,陈晓红,杨莹.等.转录因子Aiolos基因在系统性红斑狼疮中的表达[J].中华皮肤病学杂志,2010,43(7):471-473.
[18] Lessard CJ, Adrianto I, Ice JA, et al.Identification of IRF8,TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study[J].Am J Hum Genet,2012,90(4):648-660.
[19] 叶丽霞,付朝伟,江峰,等.锌指蛋白基因IKZF3多态性与中国长江以南汉族人群系统性红斑狼疮的病例对照研究[J].中华流行病学杂志,2016,37(7):996-1002.
[20] Cai X,Qiao Y,Diao C,et al. Association between polymorphisms of the IKZF3 gene and systemic lupus erythematosus in a Chinese Han population[J].PLoS One,2014,9(10):e108661.