杀伤细胞免疫球蛋白样受体基因多态性与子痫前期发病的相关性

目的 探讨杀伤细胞免疫球蛋白样受体(KIR)基因多态性(SNP)与子痫前期发病的相关性.方法 序列特异性引物PCR(PCR-SSP)技术检测子痫前期患者71例(子痫前期组)和正常孕妇100例(对照组)的外周血KIR基因型;实时荧光定量PCR技术检测两组各5例孕妇胎盘组织中KIR2DL4 mRNA的表达情况;DNA直接测序技术检测子痫前期组40例和对照组38例孕妇外周血KIR2DL4基因外显子区及其和内含子交界区的SNP.结果 (1)基因型:对照组共发现50种KIR基因型,子痫前期组共发现40种KIR基因型,两组有16种基因型重合;子痫前期组以基因型42的表达频率最高(15.5%),其次是基因型51(9.9%)和基因型47(7.0%);对照组以基因型47的表达频率最高(22.O%),其次是基因型48(11.O%).两组16种重合的KIR基因型的分布比较,差异有统计学意义(P=0.01).(2)胎盘组织KIR2DL4 mRNA的表达:子痫前期组患者胎盘组织KIR2DL4 mRNA的表达最为14.05±0.25,对照组为12.19±0.85,两组比较,差异有统计学意义(P=0.02).(3)KIR2DL4基因测序:KIR2DL4基因测序发现18个SNP位点,其中有7个为新发现的SNP位点,检测到的所有SNP位点的等位基因、基因型在两组的分布比较,差异无统计学意义(P>0.05).结论 KIR基因型可能与子痫前期的发病相关;KIR2DL4 mRNA表达量下降可能参与子痫前期的病理生理过程.

Correlation between killer cell immunoglobulin-like receptors genes and pre-eclampsia

objective To analyze the killer cell immunoglobulin-like receptors(KIR)gene polymorphism of pre-eclampsia patients and approach the correlation between KIR genes and pre-eclampsia.Methods The KIR gene polymorphisms of 71 pre-eclampsia patients and 100 healthy pregnant women were detected by PCR-SSP.The KIR2DL4 mRNA level in placentas from pre-eclampsia and gestational normal pregnancies were quantified by real time RT-PCR.Forty pre-eclampsia patients and 38 healthy pregnant women were detected for single nucleotide polymorphisms(SNP)in the gene coding and joint areas between introns and extrons by directly sequencing techniques of KIR2DL4 genomic DNA.Finally,all alleles and genotypes of KIR2DL4 gene were case-control studied.Result Distributions of some relatively activating KIR genotypes shewed a significant association with pre-eclampsia.Real-time RT-PCR showed that KIR2DL4 mRNA can be measured both in placenta of women with pre-eclampsia being of pre-eclampsia waft significantly lower than that of normal pregnancy.only as much as 0.276 times that of controls.We identified 18 polymorphisms,of which,7 were first reported.But no significant differences in genotype distributions or allele frequencies were observed in these SNPs between cases and controls.Conclusion The distributions of some relatively activating KIR genotypes showed a significant association with pre-eclampsia,which indicates that the polymorphism of KIR genes may be associated with the genetic predisposition to pre-eclampsia.And because the expression of KIR2DL4 mRNA in the placentas of cases wag significantly lower than control group,it is speculated that the decrease of KIR2DL4 expression in placenta may participate in the pathogenesis of pre-eclampsia.