Evidence that polymorphic deletion of the glutathione S-transferase gene, GSTM1, is associated with esophageal atresia

BACKGROUND: Esophageal atresia (EA) is a life‐threatening congenital condition whose etiology and pathogenesis are still poorly understood. An increasing trend of this pathology in some Italian regions suggests a possible interaction between xenobiotics and genes involved in detoxification processes during early embryonic development. For the first time polymorphisms of GSTM1, GSTT1, and GSTP1 genes were analyzed in association with EA. METHODS: The study population consisted of 25 EA children, 50 unrelated healthy children, 20 of the EA children's mothers, and 40 unrelated mothers. GSTM1 and GSTT1 null genotypes were identified by PCR amplification, and GSTP1 polymorphism was detected by RFLP analysis. RESULTS: An association was found between homozygosity for the GSTM1 null genotype and EA in affected children (p = 0.0022) and their mothers (p = 0.022). No association was found between GSTT1 and GSTP1 polymorphisms and EA children or their mothers. CONCLUSIONS: Results suggest that the GSTM1−/− null genotype may play an important role in the development of EA during early embryogenesis as a consequence of altered detoxification processes both in children and in the mothers. We hypothesize that GSTM1 allelic loss could be responsible for reduced or null catalytic activity in tissues exposed to amniotic fluid, and inefficient detoxification could be a trigger altering proliferation/apoptotic pattern of gut‐trachea separation. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.