Diagnostic value of combined detection of folate metabolism-related gene polymorphism and serum homocysteine and folate for early unexplained recurrent spontaneous abortion

Du Tingting; Li Yongjie

doi:10.3969/j.issn.1674-7151.2024.04.011

Abstract：Objective To investigate the diagnostic value of folate metabolism-related gene polymorphism combined with serum homocysteine(HCY)and folate detection for early unexplained recurrent spontaneous abortion(URSA).Methods A retrospective study model was employed.A total of 160 patients with URSA undergoing perinatal care at Xuzhou Heping Maternity Hospital from January 2022 to December 2023 were selected as study subjects.Based on the time of miscarriage,the patients were divided into early miscarriage group(80 cases;gestational age<12 weeks)and late miscarriage group(80 cases;gestational age of 12-20 weeks).Additionally,80 pregnant women undergoing routine perinatal care during the same period were selected as control group.All enrolled individuals underwent testing for serum HCY and folate levels and polymorphisms at C677T and A1298C loci of methylenetetrahydrofolate reductase(MTHFR)gene,as well as A66G locus of methionine synthase reductase(MTRR)gene.Differences in folate metabolism-related gene polymorphism and serum HCY and folate levels among the groups were compared.Multivariate Logistic regression analysis was used to identify risk factors for early URSA.The receiver operator characteristic curve(ROC curve)was plotted and the area under ROC curve(AUC)was calculated to evaluate the diagnostic value of individual and combined detection of indicators for early URSA.Results The level of HCY in early miscarriage group was significantly higher than those in late miscarriage group and control group,while the level of folate was significantly lower,with statistically significant differences[HCY(μmol/L):8.29(5.52,12.82)vs.6.69(4.27,9.77),6.92(5.48,8.16);folate(nmol/L):6.82(4.53,10.57)vs.10.79(7.87,12.84),13.04(10.24,15.80);all P<0.05].The frequencies of TT genotype and T allele at C677T locus of MTHFR gene in early miscarriage group were significantly higher than those in control group,with statistically significant differences[TT genotype:46.25%(37/80)vs.30.00%(24/80);T allele:66.88%(107/160)vs.55.00%(88/160);both P<0.05].The frequencies of CC genotype and C allele at A1298C locus of MTHFR gene in early miscarriage group were significantly higher than those in control group,with statistically significant differences[CC genotype:15.00%(12/80)vs.5.00%(4/80);C allele:33.13%(53/160)vs.20.63%(33/160);both P<0.05].High level of HCY,low level of folate,TT genotype at C677T locus of MTHFR gene and CC genotype at A1298C locus of MTHFR gene were all identified as independent risk factors for early URSA[odds ratios(OR)were 1.414,0.804,0.336 and 0.274,respectively,with 95%confidence intervals(95%CI)of 1.041-1.251,0.739-0.876,0.153-0.738 and 0.072-1.043,respectively;all P<0.05].Among the individual indicators,folate had the highest AUC for diagnosing early URSA,with a value of 0.744 and the highest sensitivity of 87.50%.CC genotype at A1298C locus of MTHFR gene had the highest specificity for diagnosing early URSA,with a value of 93.75%.Combined detection of all indicators had the highest AUC for diagnosing early URSA,with a value of 0.799.Conclusions High level of HCY,low level of folate,TT genotype at C677T locus of MTHFR gene and CC genotype at A1298C locus of MTHFR gene are all independent risk factors for early URSA.These factors have certain clinical significance in the diagnosis of early URSA and could be used for clinical auxiliary diagnosis.