Association Between TG Gene Polymorphisms With Preeclampsia

Objective:（1）To reveal the association between SNPs TG and preeclampsia.（2）To analyze the relevance between SNPs TG and clinical biochemical indexes of preeclampsia.（3）To build predictive models for preeclampsia.Objects and methods:（1）Study subjects:The women who delivered in the First Hospital of Jilin University from June 2019 to September 2021.The case-control study involved 401 patients,204pregnant women with preeclampsia were collected as case groups,which was divided into two sub-groups:early onset preeclampsia（EOPE group）97 and late onset preeclampsia（LOPE group）107,and 197 healty women who were hospitalized for delivery at the same time were selected as control groups.（2）Methods:DNA was extracted from peripheral blood of pregnant women,and single nucleotide polymorphisms（SNPs）of rs180223 and rs853326 of TG gene in peripheral blood were detected by multi-PCR second-generation DNA targeted sequencing technology.The SPSS18.0 statistical software and SNPStats website were used for statistical analysis.Firstly,the clinical indexes of pregnant women in the case group and the control groups were compared.Secondly,the association between polymorphisms of TG rs180223and rs853326 and PE susceptibility was explored;besides,the relationship between single nucleotide polymorphisms of the two SNPs and clinical biochemical indexes was analyzed.Finally,the prediction model of preeclampsia was established.P<0.05 was statistically significant between the case groups and the control groups;P<0.017 was statistically significant between the EOPE and LOPE sub-groups and the control groups.Results:（1）The comparison of clinical biochemical parameters between the case groups and sub-groups with the control groups.The PE patients with higher pre-pregnancy body mass index（BMI）,systolic pressure,diastolic pressure and mean platelet volume,mean width of platelets,thyroid stimulating hormone,serum free thyroxine,triglyceride,lower density lipoprotein cholesterol（LDL-C）,and serum creatinine than the control groups,the difference was statistically significant（P<0.05）.Gestational weeks,serum free triiodothymine,high density lipoprotein,serum calcium ion,albumin and platelet were lower than those in the control group,and the difference were statistically significant（P<0.05）.The results of each sub-group were basically the same,and the difference was statistically significant（P<0.05）.（2）Relationship between TG gene rs180223 and rs853326 SNPs and the clinical data in the case groups and its sub-groups.The distribution of TT,TG and GG genotypes of rs180223 were significantly different between EOPE and control groups（χ2=11.914,P<0.017）.There were significant differences in the distribution frequencies of AA,AG and GG of rs853326 genotype between EOPE and control groups（χ2=9.302,P<0.017）.In PE groups,thegenotype（TT+TG）groups and GG groups,the GG groups’gestational age,mean platelet volume,platelet distribution width,serum calcium and albumin levels of TG rs180223 were lower than those in genotype（TT+TG）groups,the difference was statistically significant（P<0.05）.The serum creatinine level of GG genotype was higher than that of（TT+TG）groups,and the difference was statistically significant（P<0.05）.There was no significant difference in other clinical indicators（P>0.05）.The results of TG rs853326 were basically consistent with rs180223.Moreover,the rs180223 and rs853326 were linkege disequilibrium（D’>0.75）.（3）Prediction modelIn this study,the age,pre-pregnancy body mass index,thyroid stimulating hormone,mean platelet volume and triglyceride were independent risk factors of PE,while serum calcium was a protective factor.TG rs180223 GG genotype was an independent risk factor of EOPE group.Based on age,pre-pregnancy body mass index,thyroid stimulating hormone,serum free triiodothyronine,mean platelet volume,low density lipoprotein,serum calcium ion and TGrs180223（GG）,we obtained satisfactory prediction model.The area under curve（AUC）of PE,EOPE and LOPE groups were AUC^roc=0.874（95%CI 0.840-0.907）,AUC^roc=0.914（95%CI 0.880-0.948）and AUC^roc=0.882（95%CI）,0.842-0.922)respectively.This model has clinical value,and can be used for early forecast of preeclampsia.Conclusion:（1）In this study,the age,prepregnancy body mass index,thyroid stimulating hormone,mean platelet volume and triglyceride were independent risk factors of PE,and serum calcium was a protective factor.（2）The TG SNPs of rs180223 and rs853326 may be associated with the pathogenesis of EOPE,and TG rs180223 GG genotype was an independent risk factor associated with EOPE groups.Patients with the GG genotype had higher creatinine levels and lower albumin levels,suggesting that patients with the GG gene may have more severe kidney damage.And rs180223 and rs853326 were strongly linked disequilibrium..（3）By incorporating clinical parameters and genetic information,we obtainedsatisfactory predictive models.The area under curve（AUC）of PE,EOPE and LOPE groups were AUC^roc=0.874（95%CI 0.840-0.907）,AUC^roc=0.914（95%CI0.880-0.948）and AUC^roc=0.882（95%CI0.842-0.922）respectively.This model has clinical value and can be used for early prediction of preeclampsia.