唐氏综合征高危孕妇血液中游离胎儿DNA与人绒毛膜促性腺激素β亚单位水平变化的关系

目的 探讨唐氏综合征(DS)高危孕妇血液中游离胎儿DNA(fDNA)与人绒毛膜促性腺激素β亚单位(β-hCG)水平变化的关系及意义.方法 选择2005年6月至2008年2月在山东大学附属省立医院和济南市妇幼保健院行孕中期DS筛查的单胎妊娠男胎孕妇,其中DS筛查高危且确诊为妊娠DS胎儿孕妇5例(DS组),DS筛查高危孕妇21例(DS高危组),DS筛查低危孕妇22例(对照组).提取孕妇血浆中游离fDNA,以男性DYS14基因为fDNA的标志物;采用实时定量PCR技术定量检测孕妇血浆游离fDNA含量;采用化学发光免疫分析法测定孕妇血清中β-hCG水平.比较3组孕妇血液中游离fDNA的含量与β-hCG水平,并对两者行Pearson相关性分析.结果 (1)游离fDNA含量:DS组孕妇血浆中游离fDNA含量为(127±58)GE/ml,高于DS高危组的(78±28)GE/ml和对照组的(48±21)GE/ml,分别比较,差异均有统计学意义(P<0.01);DS高危组孕妇血浆中游离fDNA含量也高于对照组,差异也有统计学意义(P<0.01).(2)β-hCG水平:DS组孕妇血清β-hCG水平为(97±43)kU/L,高于DS高危组的(58±25)kU/L和对照组的(38±19)kU/L,分别比较,差异均有统计学意义(P<0.01);DS高危组孕妇血清β-hCG水平也高于对照组,差异也有统计学意义(P<0.01).(3)游离fDNA含量与β-hCG水平的相关性:3组孕妇血浆游离fDNA含量与血清β-hCG水平均呈正相关关系(r=0.83,P<0.05;r=0.76,P<0.01;r=0.86,P<0.01).结论 孕妇血浆中游离fDNA可作为产前筛查DS的候选指标,但由于游离fDNA与β-hCG水平变化密切相关,因此其价值有待商榷.

Correlation of free fetal DNA with β-human chorionin gonadotropin in circulation in pregnant women with high-risk of Down's syndrome

Objective To investigate significance and correlation of free fetal DNA (fDNA) and β-human chorionic gonadotropin(β-hCG) in circulation in pregnant women with high-risk of Down's syndrome (DS). Methods Pregnant women with a male fetus at second trimester screening for Down's syndrome were chosen, including 5 women with a trisomy 21 fetus (DS group), 21 women with DS high-risk pregnant women (DS high-risk group) matched with 22 normal pregnant women as control group. Free fDNA in maternal plasma were extracted. Male DYS14 gene was labled as fDNA, real-time PCR was used to detect fDNA expression. The concentration of β-hCG in maternal serum was detected by chemiluminescence immune assay. The relationship between level of free fDNA and β-hCG concentration was analyzed by Pearson correlation analysis. Results (1) The mean level of free fDNA was (127±58 ) GE/ml in DS group, which was significantly higher than (78±28) GE/ml in DS high-risk group and (48±21 ) GE/ml in control group,respectively (P<0.01). When compared the level of free fDNA between DS high-risk group and control group, it reached statistical difference (P<0.01). (2) The mean concentration of β-hCG was (97±43) kU/L in DS group, which was significantly higher than (58±25) kU/L in DS high-risk group and (38±19) kU/L in control group, respectively (P<0.01). The level of β-hCG in DS high-risk group was also significantly higher than control group (P<0.01). (3) The positive relationship between the level of free fDNA in maternal plasma and β-hCG concentration in maternal serum was observed amongthree groups (r=0.83,P<0.05;r=0.76,P<0.01;r=0.86,P<0.01). Conclusions Free fDNA in maternal plasma might be a candidate marker used for prenatal DS screening. However, its clinical value need to be evaluated because of positive correlation between free fDNA and β-HCG in maternal circulation.