HLA-DRB1 alleles are associated with the susceptibility to sporadic Parkinson's disease in Chinese Han population.

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 χ(2) 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

The allele frequencies of HLA-DRB1*0301 and HLA-DRB1*0406 in populations from various ethnic regions.

<p>These data information were collected from the Allele Frequency Net Database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048594#pone.0048594-GonzalezGalarza1" target="_blank">[52]</a> except reference 25,27–30,33–34,38–39,41,45,51. Allele Frequency: Total number of copies of the allele in the population sample (Alleles/2n) in decimal format. a: data from Chinese National Marrow Donor Program(CMDP), b: data from Tzu Chi Taiwan Marrow Donor Registry (TCTMDR), c: data from USA Colorado Univ. Cord Blood Bank, d: data from Poland DKMS, e: data from Umbilical Cord Blood Bank of Bacelona, f: data in Allele frequency net was calculated from Phenotype Frequencies assuming Hardy-Weinberg proportions.</p

Comparison of the allele frequencies of HLA-DRB1*0301 among various groups.

<p>All subjects were classified by gender and age of onset of Parkinson’s disease (PD). △Pc<0.05 the allele frequency of HLA-DRB1*0301 in PD patients(total) vs. the one in healthy control(total), *Pc<0.05 the allele frequency of HLA-DRB1*0301 in PD patients (onset age ≤50) vs. the one in healthy control subgroup (onset age ≤50), # Pc<0.05 the allele frequency of HLA-DRB1*0301 in PD patients (onset age ≤50) vs. the one in PD patients (onset age >50).</p

Forest plots summarizing the Allele frequency of HLA-DRB1*0301 in Asian and European ancestry populations from various regions.

<p>The allele frequency was indicated as ES (95%CI). The distribution of HLA-DRB1*0301 was inequality in the worldwide populations, European ancestry populations presented a higher allele frequency of HLA-DRB1*0301 than African and Latin American ancestry populations and Asians (0.114 Vs. 0.071, 0.069, 0.041). In intra-Asian, Taiwanese presented a higher allele frequency of HLA-DRB1*0301 than populations in USA, mainland China, and Korea(0.091 Vs.0.054, 0.047, 0.022). However, HLA-DRB1*0301 was a rare allele in Japanese.</p

Basic information of patients with sporadic Parkinson’s disease (PD) and healthy controls.

<p>Basic information of patients with sporadic Parkinson’s disease (PD) and healthy controls.</p

Frequencies of HLA-DRB1 phenotypes and alleles in patients with Parkinson’s disease (PD) and healthy controls.

<p>Phenotype Frequency (Allele Frequency) was presented in every cell. “−”: the allele was not been detected. Phenotype Frequency: Percentage of individuals who have the allele (Individuals/N) in percentage format. Allele Frequency: Total number of copies of the allele in the population sample (Alleles/2N) in decimal format, Pc = correction of P value (Bonferroni adjustment), Pc<0.05 is considered as significant, ns = not significant. Patients had significant higher frequencies of HLA-DRB1*0301 and lower frequency of HLA-DRB1*0406 than healthy controls did.</p