The strongest association of FEV1 was at 4q24 in GSTCD (rs10516526, P = 2.18 × 10−23; Table 2 and Fig. 2b). Relatively little is known about GSTCD, but the presence of the C-terminal α-helical domain common to the glutathione S-transferase (GST) family of enzymes suggests this protein is involved in cellular detoxification by catalyzing conjugation of glutathione to products of oxidative stress14. GST enzymes also show glutathione peroxidase activity regulating the synthesis of prostaglandins and leukotrienes14. To explore the potential function of GSTCD, we conducted a protein homology search and identified homology with chloride intracellular channels 1, 3, 4, 5 and 6, suggesting a role for GSTCD beyond the GST enzyme family. Genes in the region also include INTS12 and NPNT. INTS12 associates with RNA polymerase II and mediates 3′-end processing of small nuclear RNA15.
