Abstract
Objective: Iron overload in the substantia nigra (SN) has been suggested playing a role in causing Parkinson’s disease (PD), but the underlying mechanism leading to iron accumulation is not clear. Divalent metal transporter 1 (DMT1), an endogenous transporter for ferrous iron, has been suggested being involved in iron metabolism in both animal model and PD patients. However, previous studies failed to reveal DMT1 as strong risk factor for PD patients. One reason might be that abnormal iron accumulation is not a universal pathogenesis for PD patients. This study aims to explore whether DMT1 is a risk factor for PD patients with or without iron overload. Methods: Transcranial sonography (TCS) was used to classify PD patients into two subgroups, PD with SN hyperechogenicity (SN+) and PD without SN hyperechogenicity (SN-), to study the possible association between DMT1 gene variants and iron overload in PD patients. One mutation (1303C/A) and two single nucleotide polymorphisms (SNPs) (1254T/C and IVS4 + 44C/A) of DMT1 gene were tested in 67 PD SN+ patients and 53 PD SN- patients of Southern Han Chinese population by method of polymerase chain reactionrestriction fragment length polymorphism (PCR–RFLP). Results: Distribution of Genotypes and allele frequencies of all these three sites didn’t show significant difference between PD SN+ and PD SN- patients. Haplotype analysis of 1254T/C and IVS4 + 44C/A didn’t reveal potential risk factor for iron overload. Conclusion: Our results suggested that DMT1 gene variants (1303C/A, 1254T/C and IVS4 + 44C/A) are not correlated with iron accumulation in PD patients.
Highlights
Parkinson’ disease (PD) is the most common movement disorder, characterized by degeneration of dopaminergic neurons in the substantia nigra (SN) of midbrain and the formation of intracytoplasmic inclusions called Lewy bodies (LBs) in the remaining dopaminergic neurons [1]
The pathogenesis of idiopathic PD has not been fully understood so far, but evidence suggests that abnormal aggregation of iron in SN perhaps have an important role in the etiology of idiopathic PD [2]
SN+ PD patients and SN- PD patients were well matched in age (P=0.915), gender (P=0.772), age of onset (P=0.88), UPDRS III score (P=0.106), and Hoehn-Yahr stage (P=0.77)
Summary
Parkinson’ disease (PD) is the most common movement disorder, characterized by degeneration of dopaminergic neurons in the substantia nigra (SN) of midbrain and the formation of intracytoplasmic inclusions called Lewy bodies (LBs) in the remaining dopaminergic neurons [1]. Brain iron abnormalities in SN were first observed in idiopathic PD patients about 90 years ago [3]. Subsequent studies demonstrated an increase of total iron in SN [4,5,6], where dopaminergic neurons undergo selective degeneration. Related researches showed a sensitive and stable hyperechogenicity in idiopathic PD patients [9,10]. Animal studies and post mortem analyses of human brain tissue revealed that this hyperechogenicity is associated with increased iron levels of the substantia nigra [11,12]
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