烟台地区汉族无偿献血女性杀伤细胞免疫球蛋白受体基因多态性与妊娠及妊娠女性IgG抗体效价的相关性研究

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目的:探讨杀伤细胞免疫球蛋白受体(killer cell immunoglobulin receptor,KIR)基因多态性与烟台地区汉族无偿献血女性妊娠遗传易感性关系及与妊娠女性免疫球蛋白G ( immunoglobulin G,IgG )抗A(B)抗体效价的相关性。方法:收集2016年1月至2016年12月烟台地区无偿献血女性外周血样本,随访样本2017年1月至2018年12月间妊娠状态,分为妊娠组(160例)和未妊娠组(126例)。通过聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific primer,PCR-SSP)法进行KIR基因分型。微柱凝胶法检测妊娠女性血清中其血清IgG抗A(B)抗体的效价。统计分析KIR基因频率及单倍型与妊娠遗传易感性的关系,以及与妊娠女性IgG抗A(B)抗体效价的关系。结果:在KIR基因水平,与未妊娠对照组比较,妊娠组KIR2DL5A基因频率高(48.1%比33.3%,n χ2=6.348,n P<0.05),而KIR3DL1、KIR2DS4*FUL基因频率低(86.3%比93.7%,66.9%比80.2%,n χ2值分别为4.112和6.271,n P值均<0.05),差异有统计学意义。在KIR单倍型水平,与未妊娠对照组比较,妊娠组单倍型A比例低,而单倍型B比例高(41.3%比56.4%,58.8%比43.7%,n χ2值均为6.440,n P值均<0.05),差异有统计学意义。KIR2DL2、KIR2DL5A、KIR2DL5B、KIR2DS1、KIR2DS2、KIR2DS4*DEL、KIR2DS5、KIR3DS1、KIR3DP1*FUL在血清IgG抗A(B)抗体低效价组(<64)基因频率高于高抗体效价组(≥64)(20.9%比5.4%,60.5%比33.8%,15.1%比5.4%,62.8%比37.8%,25.6%比5.4%,55.8%比33.8%,48.8%比20.3%,60.5%比33.8%,23.3%比4.1%,n χ2值分别为8.084,11.342,3.950,9.912,11.897,7.781,14.154,11.342,11.915,n P值均<0.05),而KIR2DS4*FUL基因频率在低效价组低于高效价组(51.2%比85.1%,n χ2=20.722,n P<0.05),差异有统计学意义。在KIR单倍型水平,单倍型A在低抗体效价组的比例低于高抗体效价组(18.6%比55.4%,n χ2=23.488,n P<0.05),而单倍型B在低抗体效价组比例高于高抗体效价组(81.4%比44.6%,n χ2=23.488,n P<0.05)。n 结论:KIR基因频率及单倍型与烟台地区汉族无偿献血女性妊娠及妊娠后IgG抗A(B)抗体效价相关,可为妊娠的遗传易感性和ABO系统新生儿溶血病的遗传筛查提供了新的方向。“,”Objective:To evaluate the association of killer cell immunoglobulin receptor (KIR) genes with pregnancy and immunoglobulin G (IgG )anti A (B) antibody titers in female voluntary blood donors of the Han nationality in Yantai area.Methods:Peripheral blood samples were collected from women who donated blood gratuitously from January 2016 to December 2016 from Yantai.The pregnancy status was followed up from January 2017 to December 2018, and they were divided into pregnant group and non-pregnant group.A total of 286 specimens were enrolled, including 160 pregnant cases and 126 control cases (not pregnant). KIR genotyping was performed by polymerase chain reaction-sequence specific primers (PCR-SSP). The serum titer of IgG anti A (B) antibody was detected by microcolumn gel.Statistical analyses were conducted using SPSS 18.0.Results:Compared with the control group, the frequency of KIR2DL5A was higher in the pregnant group(48.1% vs 33.3%, n χ2 value was 6.348, n P value <0.05), while the frequency of KIR3DL1 and KIR2DS4*FUL was lower in the pregnant group(86.3% vs 93.7%, 66.9% vs 80.2%, n χ2 values were 4.112 and 6.271 respectively, n P value <0.05). The proportion of KIR haplotype A in the pregnant group was significantly lower than the non-pregnant control group, while the proportion of haplotype B was significantly higher(41.3% vs 56.4%, 58.8% vs 43.7%, both n χ2 values were 6.440, n P values <0.05). The gene frequencies of KIR2DL2, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS4*DEL, KIR2DS5, KIR3DS1 and KIR3DP1*FUL were higher in the lower IgG anti A (B) antibody titer group (64) (20.9% vs 5.4%, 60.5% vs 33.8%, 15.1% vs 5.4%, 62.8% vs 37.8%, 25.6% vs 5.4%, 55.8% vs 33.8%, 48.8% vs 20.3%, 60.5% vs 33.8%, 23.3% vs 4.1%, n χ2 values were 8.084, 11.342, 3.95, 9.912, 11.897, 7.781, 14.154, 11.342, 11.915 respectively, n P values <0.05), while the gene frequencies of KIR2DS4*FUL were lower in the lower titer group than in the higher titer group (51.2% vs 85.1%, n χ2 value was 20.722, n P value <0.05). At KIR haplotype level, haplotype A was lower in lower titer group than in higher titer group(18.6% vs 55.4%, n χ2 value was 23.488, n P value <0.05), while haplotype B was higher in lower titer group than in the higher titer group(81.4% vs 44.6%, n χ2 value was 23.488, n P value <0.05).n Conclusion:KIR gene frequencies and haplotypes are correlated with pregnancy and IgG anti A (B) antibody titers in female voluntary blood donors of the Han nationality in Yantai area.The results provide a new direction for genetic screening of pregnancy susceptibility and ABO hemolytil disease of newborn.
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