[Association of maternal diabetes mellitus and UCP2 gene polymorphisms with congenital heart disease in offspring: a case-control study].

OBJECTIVE To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. METHODS A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. RESULTS After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05). CONCLUSIONS Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

[1]  Lizhang Chen,et al.  Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: an updated systematic review and meta-analysis , 2019, Archives of Gynecology and Obstetrics.

[2]  M. Soto,et al.  The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population , 2018, Genetics and molecular biology.

[3]  C. Fu,et al.  UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China , 2018, BMC Medical Genetics.

[4]  Feng Wang,et al.  [Research advances in the mechanism of congenital heart disease induced by pregestational diabetes mellitus]. , 2017, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.

[5]  E. Sönmezgöz,et al.  Role of the Polymorphisms of Uncoupling Protein Genes in Childhood Obesity and Their Association with Obesity-Related Disturbances. , 2017, Genetic testing and molecular biomarkers.

[6]  M. El-Hafidi,et al.  Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins , 2016, Oxidative medicine and cellular longevity.

[7]  Ken‐ichi Yamada,et al.  Fluorescence probes to detect lipid-derived radicals. , 2016, Nature chemical biology.

[8]  J. Priest,et al.  Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease , 2016, Circulation.

[9]  P. Tsao,et al.  Diabetic Cardiovascular Disease Induced by Oxidative Stress , 2015, International journal of molecular sciences.

[10]  L. Canani,et al.  Polymorphisms of the UCP2 Gene Are Associated with Glomerular Filtration Rate in Type 2 Diabetic Patients and with Decreased UCP2 Gene Expression in Human Kidney , 2015, PloS one.

[11]  A. G. Gittenberger-de Groot,et al.  N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes , 2014, Cardiovascular Diabetology.

[12]  Shiliang Liu,et al.  Association Between Maternal Chronic Conditions and Congenital Heart Defects: A Population-Based Cohort Study , 2013, Circulation.

[13]  A. Olshan,et al.  Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study. , 2012, American journal of epidemiology.

[14]  S. Vollset,et al.  Congenital anomalies in newborns of women with type 1 diabetes: nationwide population‐based study in Norway, 1999–2004 , 2010, Acta obstetricia et gynecologica Scandinavica.

[15]  K. Rothman,et al.  A Prospective Study of the Risk of Congenital Defects Associated with Maternal Obesity and Diabetes Mellitus , 2000, Epidemiology.

[16]  A. Gilchrist Congenital Heart Disease , 1948, Edinburgh medical journal.

[17]  J. Pincemail,et al.  [Oxidative stress]. , 2007, Revue medicale de Liege.