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. 2022 Nov 5;12(11):2705.
doi: 10.3390/diagnostics12112705.

HtrA1 in Gestational Diabetes Mellitus: A Possible Biomarker?

Giovanni Tossetta  1   2 , Sonia Fantone  1 , Rosaria Gesuita  3 , Gian Carlo Di Renzo  4   5 , Arun Meyyazhagan  5 , Chiara Tersigni  6   7 , Giovanni Scambia  6   7 , Nicoletta Di Simone  8   9 , Daniela Marzioni  1
Affiliations

HtrA1 in Gestational Diabetes Mellitus: A Possible Biomarker?

Giovanni Tossetta et al. Diagnostics (Basel). .

Abstract

Background: The high-temperature requirement A 1 (HtrA1) is a multidomain secretory protein with serine-protease activity, expressed in many tissues, including placenta, where its expression is higher in the first trimester, suggesting an association of this serine protease in early phases of human placenta development. In this study, we evaluated maternal serum HtrA1 levels in the first and third trimester of gestation. In particular, we evaluated a possible role of HtrA1 as an early marker of gestational diabetes mellitus (GDM) in the first trimester of gestation.

Methods: We evaluated HtrA1 serum levels in the third trimester (36-40 weeks) in normal pregnancies (n = 20) and GDM pregnancies (n = 20) by using ELISA analysis. Secondly, we performed the same analysis by using the first trimester sera (10-12 weeks) of healthy pregnant women that will develop a normal pregnancy (n = 210) or GDM (n = 28) during pregnancy.

Results: We found that HtrA1 serum levels in the third trimester were higher in pregnancies complicated by GDM. Interestingly, higher HtrA1 serum levels were also found in the first trimester in women developing GDM later during the second-third trimester. No significant differences in terms of maternal age and gestational age were found between cases and controls. Women with GDM shown significantly higher pre-pregnancy BMI values compared to controls. Moreover, the probability of GDM occurrence significantly increased with increasing HtrA1 levels and BMI values. The ROC curve showed a good accuracy in predicting GDM, with an AUC of 0.74 (95%CI: 0.64-0.92).

Conclusions: These results suggest an important role of HtrA1 as an early predictive marker of GDM in the first trimester of gestation, showing a significative clinical relevance for prevention of this disease.

Keywords: GDM; HtrA1; first trimester; marker; pregnancy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Women’s demographic and clinical characteristics according to health status at the first trimester of gestation. p-values refer to Wilcoxon rank sum test.
Figure 2
Figure 2
Observed and smoothed ROC curves with 95% confidence interval for the predictiveness of GDM. Grey area identifies 95% confidence interval of ROC. AUC: Area Under Curve; 95%CI: 95% Confidence Interval. ROC was estimated as a function of HtrA1 type of nutrition in the third trimester of gestation and BMI before pregnancy.
See this image and copyright information in PMC

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