ABSTRACT
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.
Subject(s)
Blood Glucose/genetics , Genetic Association Studies/methods , Insulin Resistance/physiology , Iodide Peroxidase/genetics , Placenta/physiology , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Alanine/genetics , Blood Glucose/metabolism , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Middle Aged , Pregnancy , Pregnancy Outcome/epidemiology , Threonine/genetics , Young Adult , Iodothyronine Deiodinase Type IIABSTRACT
Metarhizium anisopliae infects arthropods via a combination of specialized structures and cuticle degradation. Hydrolytic enzymes are accepted as key factors for the host penetration step and include chitinases. The characterization of the chi2 chitinase gene from M. anisopliae var. anisopliae is reported. The chi2 gene is interrupted by two short introns and is 1,542-bp long, coding a predicted protein of 419 amino acids with a stretch of 19 amino acid residues displaying characteristics of signal peptide. The predicted chitinase molecular mass is 44 kDa with a mature protein of 42 kDa and a theoretical pI of 4.8. The comparison of the CHI2 predicted protein to fungal orthologues revealed similarity to the glycohydrolase family 18 and a phylogenetic analysis was conducted. The chi2 gene is up-regulated by chitin as a carbon source and in conditions of fungus autolysis, and is down-regulated by glucose. This regulation is consistent with the presence of putative CreA/Crel/Crr1 carbon catabolic repressor binding domains on the regulatory sequence.
