Fcγ受体ⅢB基因多态性与系统性红斑狼疮易感性及临床表型的相关性研究

Association of Fcgamma receptorⅢB gene polymorphism with susceptibility and clinical phenotypes of systemic lupus erythematosus

目的研究Fcγ受体ⅢB基因多态性在黄河三角洲汉族人群中的分布,探讨其多个位点的基因多态性与SLE易感性及临床表型的相关性。方法选择2017年1月至12月于山东省滨州医学院附属医院就诊的144例SLE患者作为试验组,同期健康志愿者150名作为对照组,收集全血标本和临床资料、试验室检查资料,采用单碱基延伸法PCR技术提取基因组脱氧核糖核酸(DNA),采用质谱法进行单核苷酸多态性(SNP)分型检测,应用SPSS 25.0软件进行χ^2检验,分析Fcγ受体ⅢB基因各位点基因多态性与SLE易感性及临床表型的关系。结果①在试验组和对照组中,rs115878669 CT、TT基因型频率分别为50.7%、64.0%,23.6%、10.0%,差异有统计学意义(χ^2=5.3,P=0.021;χ^2=9.8,P=0.002);rs147574249 TT基因型频率分别为17.4%、8.0%,差异有统计学意义(χ^2=5.9,P=0.016);rs199705513 GG、GA基因型频率分别为20.8%、10.0%,59.0%、70.0%,差异有统计学意义(χ^2=6.7,P=0.010;χ^2=3.9,P=0.049);rs77717968 CA基因型频率分别为30.6%、46.0%,差异有统计学意义(χ^2=7.4,P=0.007)。②在试验组中,rs115878669位点杂合子CT基因型频率在血液系统受累和不受累组分别为37.2%、56.4%,差异有统计学意义(χ^2=4.5,P=0.035);在血小板减少组与血小板正常组中,rs114531649位点AG基因型频率分别为79.2%、50.0%,差异有统计学意义(χ^2=6.8,P=0.009),GG基因型频率分别为4.2%、25.8%,差异有统计学意义(χ^2=4.3,P=0.039),rs147574249位点CC基因型频率分别为4.2%、25.8%,差异有统计学意义(χ^2=5.4,P=0.020),CT基因型频率分别为79.2%、56.7%,差异有统计学意义(χ^2=4.2,P=0.040),rs115878669位点CT基因型频率分别为70.8%、46.7%,差异有统计学意义(χ^2=4.7,P=0.031),rs199705513位点AA基因型频率分别为4.2%、23.3%,差异有统计学意义(χ^2=4.6,P=0.033),rs77717968位点AA基因型频率分别为4.2%、26.7%,差异有统计学意义(χ^2=4.5,P=0.033),TT基因型频率分别为25.0%、9.2%,差异有统计学意义(χ^2=4.8,P=0.028),其他比较无统计学意义(P>0.05)。在关节受累组与关节未受累组中,rs114531649位点纯合子GG基因型频率分别为31.2%、15.7%,差异有统计学意义(χ^2=4.9,P=0.027),rs147574249位点纯合子CC基因型频率分别为31.2%、15.7%,差异有统计学意义(χ^2=4.9,P=0.027),rs199705513位点纯合子AA基因型频率分别为29.5%、13.2%,差异有统计学意义(χ^2=5.8,P=0.016),rs61803007位点纯合子CC基因型频率分别为32.8%、16.9%,差异有统计学意义(χ^2=4.9,P=0.026),杂合子TC基因型频率分别为67.2%、83.1%,差异有统计学意义(χ^2=4.9,P=0.026),rs77717968位点纯合子AA基因型频率分别为31.2%、16.9%,差异有统计学意义(χ^2=4.1,P=0.044),其他比较差异无统计学意义(P>0.05)。rs146653557位点杂合子TC基因型基因型频率在有浆膜炎组和无浆膜炎组分别为39.4%、75.0%,差异有统计学意义(χ^2=4.3,P=0.037),其他比较差异无统计学意义(P>0.05)。在RF升高组与RF未升高组中,rs428194位点CG基因型频率分别为53.8%、22.9%,差异有统计学意义(χ^2=12.7,P=0.0004),GG基因型频率分别为46.2%、77.1%,差异有统计学意义(χ^2=12.7,P=0.0004),rs61803004位点GG基因型频率分别为46.2%、78.1%,差异有统计学意义(χ^2=13.7,P=0.0002),GT基因型频率分别为46.2%、21.0%,差异有统计学意义(χ^2=9.0,P=0.0027),TT基因型频率分别为7.7%、1.0%,差异有统计学意义(χ^2=4.8,P=0.029),rs61803008位点CT基因型频率分别为46.2%、23.8%,差异有统计学意义(χ^2=6.8,P=0.0092),TT基因型频率分别为46.2%、74.3%,差异有统计学意义(χ^2=10.1,P=0.0015)。结论Fcγ受体ⅢB基因相关位点可能与SLE的疾病易感性及临床表型有关。

Objective To study the distribution of FCγreceptorⅢB gene polymorphism in the Han population in the Yellow River Delta,and to explore the correlation between the gene polymorphism of multiple loci and the susceptibility and clinical phenotypes of systemic lupus erythematosus(SLE).Methods From January 2017 to December 2017,144 SLE patients in the Affiliated Hospital of Binzhou Medical College of Shandong Province were selected as the experimental group and 150 healthy people as the control group.Whole blood samples,clinical data and laboratory examination test data were collected.Genomic DNA was extracted by single base extension polymerase chain reaction(PCR)technology and single nucleoside was extracted by mass spectrometry.The relationship between the polymorphism of each point of FCγreceptorⅢB gene and the susceptibility and clinical phenotypes of SLE was analyzed byχ^2 test with SPSS 25.0 software.Results①The frequencies of CT and TT genotype at rs115878669 were 50.7%,64.0%,23.6%and 10.0%respectively in the test group and the control group,the difference was statistically significant(χ^2=5.3,P=0.021;χ^2=9.8,P=0.002);The frequencies of TT genotype at rs147574249 were 17.4%and 8.0%respectively in the test group and the control group,the difference was statistically significant(χ^2=5.9,P=0.016);The frequencies of GG and GA genotype at rs199705513 were 20.8%,10.0%,59.0%,70.0%,the difference was statistically significant(χ^2=6.7,P=0.010;χ^2=3.9,P=0.049);The frequency of CA genotype at rs77717968 was 30.6%and 46.0%in the test group and the control group,respectively,the difference was statistically significant(χ^2=7.4,P=0.007).②In the experimental group,the frequencies of heterozygous CT genotypes at rs115878669 were 37.2%and 56.4%in the blood system affected group and the unaffected group,respectively,the difference was statistically significant(χ^2=4.5,P=0.035).In the thrombocytopenia group and the normal platelet normal count group,the frequencies of AG genotypes at rs114531649 were 79.2%and 50.0%,respectively,the difference was statistically significant(χ^2=6.8,P=0.009)and GG genotypes were 4.2%and 25.8%.The difference was statistically significant(χ^2=4.3,P=0.039).The frequency of CC genotype at rs147574249 was 4.2%,25.8%respectively.The difference was statistically significant(χ^2=5.4,P=0.020).The frequency of CT genotype was 79.2%,56.7%respectively.The difference was statistically significant(χ^2=4.2,P=0.040).The frequency of CT geno-type at rs115878669 was 70.8%,46.7%,respectively.The difference was statistically significant(χ^2=4.7,P=0.031).The frequency of AA genotype at rs199705513 was 4.2%,and 23.3%,the difference was statistically significant(χ^2=4.6,P=0.033),the frequency of AA genotype at rs77717968 was 4.2%,26.7%,and the difference was statistically significant(χ^2=4.5,P=0.033),the frequency of TT genotype was 25.0%,9.2%,the difference was statistically significant(χ^2=4.8,P=0.028).There was no statistical significance difference in other comparisons(P>0.05).The GG genotype frequencies of rs114531649 and the CC genotype frequencies of rs147574249 were 31.2%and 15.7%,respectively.The differences were statistically significant(χ^2=4.9,P=0.027).The AA geno-type frequencies of rs199705513 were 29.5%and 13.2%,the difference was statistically significant(χ^2=5.8,P=0.016),the CC genotype frequency of homozygote at rs61803007 was 32.8%,16.9%,the difference was statistically significant(χ^2=4.9,P=0.026),the TC genotype frequency of heterozygote was 67.2%,83.1%,the difference was statistically significant(χ^2=4.9,P=0.026),the AA genotype frequency of homozygote at rs77717968 was 31.2%,16.9%,respectively,the difference was statistically significant(χ^2=4.1,P=0.044),and there was no significant difference in other comparisons(P>0.05).The frequency of TC genotype in rs146653557 was 39.4%in serositis group and 75.0%in non serositis group,the difference was statistically significant(χ^2=4.3,P=0.037),the other differences were not statistically significant(P>0.05).The frequency of CG genotype in rs428194 group and rs61803004 group was 53.8%and 22.9%respectively,the difference was statistically significant(χ^2=12.7,P=0.0004).The frequency of GG genotype in rs428194 group was 46.2%and 77.1%,46.2%and 78.1%in rs61803004 group respectively,the difference was statistically significant(χ^2=12.7,P=0.0004;χ^2=13.7,P=0.0002).The frequencies of GT genotype were 46.2%and 21.0%.The differences were statistically significant(χ^2=9.0,P=0.0027).The frequency of TT genotypes was 7.7%and 1.0%,the difference was statistically significant(χ^2=4.8,P=0.029).The frequencies of CT genotypes at rs61803008 were 46.2%and 23.8%respectively,the difference was statistically significant(χ^2=6.8,P=0.0092).The frequencies of TT genotypes were 46.2%and 74.3%.The difference was statistically significant(χ^2=10.1,P=0.0015).Conclusion There is a significant correlation between Fc gamma receptorⅢB gene related loci and SLE susceptibility and clinical phenotypes.