Interactions between plasma copper concentrations and SOD1 gene polymorphism for impaired glucose regulation and type 2 diabetes

AIMS: To examine the associations of plasma copper concentrations and superoxide dismutase 1 (SOD1) polymorphisms as well as their gene-environment interaction with newly diagnosed impaired glucose regulation (IGR) and type 2 diabetes (T2D). METHODS: We performed a large case-control study in 2520 Chinese Han subjects: 1004 newly diagnosed T2D patients, 512 newly diagnosed IGR patients and 1004 individuals with normal glucose tolerance. RESULTS: After multivariable adjustment, the ORs (95% CIs) of T2D across tertiles of plasma copper were 1.00 (reference), 1.85 (95% CI: 1.39, 2.45), and 4.21 (95% CI: 3.20, 5.55) (P-trend < 0.001). Each SD increment of ln-transformed plasma copper was associated with 104% higher odds (OR 2.04, 95%CI 1.82–2.28) increment in ORs of T2D. Meanwhile, compared with the GG genotype of rs2070424, the OR of T2D associated with AG and AA genotypes were 1.44 (95% CI 1.15–1.81) and 1.74 (95% CI 1.33–2.28), respectively. In addition, the positive association between plasma copper and T2D was modified by rs2070424 genotypes. The adjusted ORs and 95% CIs of T2D per SD increment of ln-transformed plasma copper were 2.40 (1.93–2.99), 1.85 (1.59–2.16) and 1.76 (1.44–2.15) in rs2070424 GG, AG and GG carriers respectively (P for interaction < 0.05). Similar interactions were also found for IGR and IGR&T2D. When the joint effects were examined, individuals with rs2070424 AA genotype and the highest tertile of plasma copper concentration had a much higher risk of IGR&T2D (OR 5.34, 95% CI 3.48–8.21) than those with rs2070424 GG genotype and the lowest tertile of plasma copper concentrations. CONCLUSIONS: Plasma copper concentrations are positively and significantly associated with IGR as well as T2D, and these associations may be modified by SOD1 polymorphism. Further studies are warranted to elucidate the potential mechanisms.