Haptoglobin phenotype modifies serum iron levels and the effect of smoking on Parkinson disease risk.
INTRODUCTION
Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk.


METHODS
The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk.


RESULTS
PD cases had lower serum iron than controls (83.28 ug/100 ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity.


CONCLUSIONS
Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated.
['Costa-Mallen|Paola|P|', 'Zabetian|Cyrus P|CP|', 'Agarwal|Pinky|P|', 'Hu|Shu-Ching|SC|', 'Yearout|Dora|D|', 'Samii|Ali|A|', 'Leverenz|James B|JB|', 'Roberts|John W|JW|', 'Checkoway|Harvey|H|']
D000367:Age Factors D000368:Aged D000704:Analysis of Variance D005260:Female D005293:Ferritins D006242:Haptoglobins D006801:Humans D007501:Iron D008297:Male D008875:Middle Aged D016017:Odds Ratio D010300:Parkinson Disease D010641:Phenotype D012307:Risk Factors D012737:Sex Factors D012907:Smoking
Haptoglobin phenotype Serum iron Idiopathic Parkinson disease Serum ferritin Tobacco smoking