A functional variant in the thrombospondin-1 gene and the risk of small for gestational age infants

Introduction:Thrombospondin-1 (TSP-1) is a prothrombotic and anti-angiogenic glycoprotein expressed in the placenta. A functional single nucleotide polymorphism in the TSP-1 gene (TSP-1 A2210G) is a risk factor for familial premature myocardial infarction. Small for gestational age (SGA) infants are at increased risk of coronary artery disease in adult life and common genetic factors may underlie both conditions. We investigated the association of TSP-1 A2210G in SGA infants and their parents. Method:The 3234 nulliparous pregnant women, their partners and babies were recruited in Adelaide and Auckland to a prospective multicenter cohort study. Amongst 2123 Caucasian women, 216 (10.2%) delivered an SGA infant, defined as birth weight <10th customized centile adjusted for maternal height, weight, parity and ethnicity, as well as gestational age at delivery and infant sex. Uncomplicated pregnancies served as controls (n=1185). DNA extracted from peripheral/cord blood or buccal swabs was genotyped using Sequenom MassARRAY. Multivariable logistic regression was used to compare the odds of SGA between the genotype groups adjusting for potential confounders. Results:Paternal (adjOR, 1.4; 95% CI 1.0-2.0) and neonatal (adjOR, 1.8; 95% CI, 1.1-2.7) TSP-1 A2210G associates with SGA. The maternal polymorphism approaches significance for an association with SGA (adjOR, 1.3; 95% CI, 0.9-1.9). Maternal TSP-1 A2210G associates with a reduced maternal birth weight adjusted for gestational age at delivery (P=0.03). Conclusion:The TSP-1 A2210G polymorphism, which is a risk factor for myocardial infarction, is associated with SGA pregnancies, suggesting that this polymorphism may associate with the risk of vascular disorders across the life course.