Retinopathy in pregnancy in women with type 1 diabetes - a study of associations with arterial wall elasticity and mutation in coagulation genes

Abstract

Aim: The arterial wall elasticity and genetic setting is a potential risk factor for dysfunction of vas¬cular endothelial cells and the clinical expression of retinopathy. The prevalence was evaluated of polymorphism in the genes of methylene-tetrahydro-folate-reductase (MTFHR), Factor V, glycoprotein IIb/IIIa (Gp2b3a), and prothrombin in a cohort of pregnant women with type 1 diabetes. The role of hyperhomo¬cysteinemia in microangiopathy in diabetes mellitus has been debated and is mainly seen with reduced activity of the MTHFR gene. The arterial resistance index (AASI) has been used to detect arterial dysfunction and correlate with cardiovascular morbidity and mortality in patients with hypertension.Design: Two-hundred-and-thirty-three women with type 1 diabetes mellitus were analyzed for MTHFR gene polymorphism and Factor V Leiden. In 176 of these women AASI was further evaluated. In a sub-cohort of 40 women with preeclampsia, mutations in glycoprotein IIb/IIIa (Gp2b3a) and prothrombin was measured. The pregnancy and ophthalmological examination data charts were reviewed retrospectively.Results: Retinopathy was associated with higher AASI during pregnancy (p<0.01, in all three trimesters) and preeclampsia (p<0.05). The stiffness increased with higher grades of retinopathy. AASI in women with simplex and proliferative retinopathy followed different patterns during the three trimesters, even when adjusted for age, BMI, and glycemic regulation (p<0.01). None of the studied coagulation genes (MTHFR, Factor V, Gp2b3a, and prothrombin) were found associated with retinopathy or preeclampsia. Conclusion:Retinopathy showed a strong association with AASI during pregnancy and not outside pregnancy in women with type 1 diabetes. This suggests a pregnancy-related functional change in the vascular bed.A common polymorphism in methylene-tetrahydro-folate-reductase (MTFHR 677C>T, a C to T substitution at nucleotide 677, which converts alanine to a valine residue) has been identified as responsible for reduced MTHFR activity and increased plasma homocysteine [10,11].Factor V Leiden is a mutated form of human factor V that causes an increase in blood clotting. With this mutation, the anticoagulant protein secreted is inhibited, leading to an increased tendency to form dangerous, abnormal blood clots. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst ethnic Europeans and linked with increased risk of preeclampsia, abortions, intrauterine growth restriction, placental abruption, and thrombosis [12][13][14].Glycoprotein IIb/IIIa (Gp2b3a, also known as integrin αIIbβ3) is a complex found on platelets. It is a receptor for fibrinogen and von Lauszus FF (2017) Retinopathy in pregnancy in women with type 1 diabetes -a study of associations with arterial wall elasticity and mutation in coagulation genes