Smoking and haptoglobin phenotype modulate serum ferritin and haptoglobin levels in Parkinson disease

The phenotype Hp 2-1 of haptoglobin has been previously associated with increased risk of Parkinson disease (PD) and with serum iron abnormalities in PD patients. Tobacco smoking has been consistently observed in epidemiology studies to be inversely related to PD risk, with mechanisms that remain uncertain. We recently observed that the protective effect of smoking on PD risk is stronger among subjects of haptoglobin Hp 2-2 and Hp 1-1 phenotypes, and weaker among subjects of haptoglobin Hp 2-1 phenotype. In this PD case-control study, we investigated whether tobacco smoking was associated with changes in serum haptoglobin and ferritin concentration that depended on haptoglobin phenotype among 106 PD patients and 238 controls without PD or other neurodegenerative disorders. Serum ferritin concentration, serum haptoglobin concentration, haptoglobin phenotype, and smoking data information of cases and controls were obtained. Differences in haptoglobin and ferritin concentration by smoking status and pack-years of smoking were calculated as well as regression between pack-years and haptoglobin and ferritin concentration, and the effect of haptoglobin phenotype on these parameters. Tobacco smoking was associated with an elevation in serum haptoglobin concentration, especially among healthy controls of haptoglobin Hp 2-2 phenotype, and with an elevation in ferritin concentration especially among PD patients of haptoglobin Hp 2-1 phenotype. These findings suggest that an elevation in haptoglobin concentration, preferentially among subjects of haptoglobin Hp 2-2 phenotype, could be a contributing factor to the protective effect of smoking on PD risk.