The functional polymorphism of the hemoglobin-binding protein haptoglobin influences susceptibility to idiopathic Parkinson's disease.

Abstract

Oxidative stress and iron have been widely implicated in the etiology of Parkinson's disease (PD). Hemoglobin is the richest source of iron in the body. The human Haptoglobin (Hp) protein is a plasma alpha-2 glycoprotein that removes free Hemoglobin from the circulation and tissues and is important in protection from oxidative stress, in immune system regulation, and angiogenesis. A common genetic polymorphism of Hp exists in the population, where the Hp 1-1, Hp 2-1, and Hp 2-2 forms exhibit profound functional differences. In this study, the Hp genotype corresponding to phenotypes Hp 1-1, 2-1 and 2-2 was determined in 312 idiopathic PD patients and 420 normal control subjects. A significant increase in the number of subjects carrying the Hp 2-1 genotype was present among PD patients. The distribution of Hp genotypes among PD patients (16.0% Hp 1-1, 56.4% Hp 2-1, 27.6% Hp 2-2) was significantly different from the distribution in controls (15.2% Hp 1-1, 48.1% Hp 2-1, 36.7% Hp 2-2) (chi(2) = 6.99, P = 0.030). The odds ratios for PD risk for Hp 2-1 and Hp 1-1 versus Hp 2-2 genotype were 1.51 (1.07-2.12) and 1.36 (0.86-2.15), respectively. Overall, the association of Hp-1 allele with PD resulted stronger among subjects who were never-smokers as compared to ever-smokers. Also, among ever-smokers, Hp genotypes were significantly associated with PD only among women, but not men, indicating the presence of a gene x gender x smoking interaction. To our knowledge, this is the first study that investigates the association of Hp genotypes with the risk of PD.

• Authors: Paola Costa-Mallen, Harvey Checkoway, Aram Zabeti, Michael J Edenfield, Phillip D Swanson, W T Longstreth Jr, Gary M Franklin, Terri Smith-Weller, Sayed M H Sadrzadeh
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 147B Issue 2 Pg. 216-22 (Mar 05 2008) ISSN: 1552-485X [Electronic] United States
• PMID: 17918239 (Publication Type: Journal Article)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• HP protein, human
• Haptoglobins

Topics

• Adult
• Aged
• Aged, 80 and over
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Genotype
• Haptoglobins (genetics)
• Humans
• Male
• Middle Aged
• Parkinson Disease (genetics)
• Phenotype
• Polymorphism, Genetic
• Smoking