The pathophysiologies of bronchopulmonary dysplasia (BPD) are inflammation, infection, tissue damage, angiogenesis defects and genetic susceptibility. Because of the role of the vitamin D binding protein (Gc globulin) on these factors, we investigated the relationship between Gc globulin polymorphisms and BPD. This case-control study was performed with 160 neonates (⩽32 gestational ages, ⩽1500 g). PCR DNA sequence analyses were used for GC gene rs4588 and rs7041 single-nucleotide polymorphisms. In the univariate analyses, it was observed that Gc2 was the only variant that was protective against BPD (Odd ratio (OR)=0.47, 95% coinfidence interval (CI)=0.24 to 0.89, P=0.020). In the multivariate analyses, Gc2 decreased the risk of disease (OR=0.15, 95% CI=0.029 to 0.79, P=0.026) independent of gestational age, birth weight, 5-min Appearance, Pulse, Grimace, Activity, and Respiration scores, respiratory distress syndrome and sepsis. The Gc2 variant was, after adjusting for confounders, associated with a decrease in the frequency of BPD. Our study adds Gc globulin to the list of candidate genes that potentially contribute to the etiology of the disease.