Role Of GCLC Variants In Preeclampsia In Chinese Han Population

PE is one of the most severe complications in pregnancy,which is the most cause of maternal and fetal death.Lack of effective means of prevention and special treatments,symptomatic treatment and termination of pregnancy are mainly used in clinical salvage.It has been proved that multiple molecular mechanisms related to systemic oxidative stress are involved in PE.Researches show glutathione(GSH)plays a vital function in PE related to systemic oxidative stress.The glutamate–cysteine ligase(GCL),including a catalytic subunit(GCLC)and a regulatory subunit(GCLM),is the rate-limiting enzyme for the synthesis of GSH.The GCLC performs all of the catalytic activity of the GCL,and it is the first rate-limiting step in the synthesis of GSH.It is reported that Preeclampsia may be a complex genetic disease,and many researchers have studied the susceptibility genes of preeclampsia,and confirmed the genetic susceptibility of the disease,the single nucleotide polymorphism,SNP may modulate the expression of GCLC as well as the activity of the protein,then influence the role of GSH in systemic oxidative stress.Therefore,our study is to investigate the association between genetic variations in GCLC and the susceptibility to PE in Chinese Han population and prove an early screening and preventing measure.ObjectiveThe purpose of our study is to investigate the association between GCLC(rs17883901)and the susceptibility to PE in Chinese Han population.Methods1001 preeclampsia and 1182 cases of normal pregnant women(control group)were randomly selected from obstetric experimental specimens library,including mild PE 189 cases,severe PE 812 cases,446 cases of early-onset and late-onset 366 cases.The experimental dates were representatively tested by Hardy-Weinberg balance test.Taq Man allelic discrimination real-time PCR was adopted to analysis the polymorphism loci GCLC rs17883901 and Pearson Chi-Square test was used to analyze the statistical differences of genetic distributions between the two groups.Results(1)Our result showed that no statistical difference was found between PE and control group(c2=2.201,p=0.333 by genotypic,c2=0.524,p=0.469,OR=0.932,95%CI=0.771-1.128 by allelic).(2)there was significant difference of genotype between the control group and the mild PE patients(c2=6.999,p=0.030).(3)Compared with the control group,there was significant difference in the genotype of the patients with severe late-onset PE(c2=6.698,p=0.035).(4)Compared with the control group,there were no significant differences in allele frequencies of mild PE and severe late-onset PE(mild PE: c2=0.023,p=0.879,OR=0.974,95%CI=0.689-1.375;the severe late-onset PE:c2=0.001,p=0.976,OR=1.004,95%CI=0.773-1.304).(5)No significant differences in genotypic and allelic frequencies were found at the polymorphic sites between the severe early-onset PE and the control group(c2=0.60,P=0.741 by genotypic;c2=0.012,p=0.497,OR=1.09,95%CI=0.850-1.398 by allelic).ConclusionGCLC may be involved in the development of mild PE and late–onset PE in Chinese Han population.