Type 2 deiodinase Thr92Ala polymorphism is associated with disrupted placental activity but not with dysglycemia or adverse gestational outcomes: A genetic association study

摘要

Objective To study whether the D2 Thr92Ala polymorphism - a genetic marker that is associated with reduced thyroid type 2 deiodinase (D2) activity, increased insulin resistance, and risk for type 2 diabetes - is associated with disrupted placental D2 activity and with glycemic control and gestational outcomes. Design Cross-sectional study. Setting Tertiary hospital in Brazil. Patient(s) Consecutive singleton-pregnancy patients, 18-45 years old. Intervention(s) Clinical examination and genotyping of the D2 Thr92Ala polymorphism, with placental samples collected and assayed for D2 mRNA and activity. Main Outcome Measure(s) Glucose homeostasis and gestational outcomes. Result(s) A total of 294 patients were included in the study. The clinical and laboratory characteristics were similar among the D2 genotypes. No differences were observed in D2 placental mRNA levels, but D2 activity was decreased in patients with the Ala92Ala genotype (0.35 ± 0.15 vs. 1.96 ± 1.02 fmol/mg/min.). Newborn serum thyroid-stimulating hormone levels (TSHneo) did not differ according to maternal D2 Thr92Ala genotype. Also, maternal glucose control, insulin resistance evaluated by the homeostasis model assessment (HOMA-IR), and gestational outcomes did not differ across D2 genotypes. Conclusion(s) The D2 Ala92Ala genotype is associated with reduced placental D2 activity but is not associated with dysglycemia, increased insulin resistance, or worse gestational outcomes.