Abstract

Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The χ2 test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate.

Highlights

  • Parkinson’s disease (PD), the second most common human neurodegenerative disease, is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN) and other brainstem nuclei [1]

  • Using stratification analyses and unconditional logistic regression analysis adjusted for gender, we found that the positive association between human leucocyte antigen (HLA)-DRB1*0301 and PD risk was independent of onset age(onset age #50:odds ratio (OR) = 3.350, P = 4.039E-4, onset age .50: OR = 1.726, P = 0.007)

  • We found that HLA-DRB1 alleles may be contributing to susceptibility to sporadic PD in the Chinese Han population in the Guangdong Province of People’s Republic of China (PRC)

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Summary

Introduction

Parkinson’s disease (PD), the second most common human neurodegenerative disease, is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN) and other brainstem nuclei [1]. The exact etiology of sporadic PD still remains unknown. Immune dysfunctions have been confirmed to be one of the causes of this disease [2,3,4]. The HLA-DR antigen, encoded by HLA-DRA and HLA-DRB alleles, belongs to HLA class II molecules and acts as an antigen-presenting molecule or regulatory molecule involved in the specific immune response and innate immune response [6]. The highly polymorphic HLA complex plays an important role in genetic susceptibility to human diseases, and different alleles of HLA loci are responsible to variable immune responses among individuals [7]

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