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. 2021 Apr 28;5(2):16-26.
doi: 10.29245/2578-3009/2021/2.1209.

Immunogenetic Epidemiology of Dementia and Parkinson's Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

Lisa M James  1   2   3 , Apostolos P Georgopoulos  1   2   3   4
Affiliations

Immunogenetic Epidemiology of Dementia and Parkinson's Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

Lisa M James et al. J Immunol Sci. .

Abstract

Human leukocyte antigen (HLA), which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson's disease. Here we report on the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of dementia and Parkinson's disease in 14 Continental Western European countries, extending previous work1,2. We used these correlations to construct and compare HLA profiles for each disease3. We found that (a) the HLA profiles of the two diseases were significantly correlated across both HLA Class I and Class II alleles, (b) negative ("protective") HLA-disease correlations did not differ significantly for either HLA class, but (c) positive ("susceptibility") HLA-disease correlations were significantly higher in dementia than in Parkinson's disease for both HLA classes of alleles. These findings indicate that (a) dementia and Parkinson's disease share immunogenetic HLA-related mechanisms, (b) HLA-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c) HLA-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson's disease.

Keywords: Dementia; Genetics; Human leukocyte antigen; Immunity; Parkinson’s disease.

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Conflict of interest statement

Conflicts of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1.
Figure 1.. Example from a presumed protective HLA allele.
Dementia prevalence for 13 CWE countries (for which DRB1*04:01 frequency was available) is plotted against the corresponding DRB1*04:01 allele frequency in the original (percentage) dementia prevalence scale (A) and its natural log transformed values (B). The fitted line is an exponential function (A) that becomes a linear function in the log-transformed prevalence scale (B). The statistics for the linear case are: Pearson correlation r = −0.877, P < 0.0001; r'=atanh(r) = −1.363.
Figure 2.
Figure 2.. Example from a presumed susceptibility HLA allele.
Dementia prevalence for 11 CWE countries (for which DPB1*02:01 frequency was available) is plotted against the corresponding DPB*02:01 allele frequency in the original (percentage) dementia prevalence scale (A) and its natural log transformed values (B). The fitted line is an exponential function (A) that becomes a linear function in the log-transformed prevalence scale (B). The statistics for the linear case are: Pearson correlation r = −0.805, P = 0.003; r'=atanh(r) = 1.112.
Figure 3.
Figure 3.. Frequency distribution of HLA profiles for Parkinson’s disease.
N = 68 alleles for Class I and 59 alleles for Class II.
Figure 4.
Figure 4.. Frequency distribution of HLA profiles for dementia.
N = 68 alleles for Class I and 59 alleles for Class II.
Figure 5.
Figure 5.. The HLA profile (r') of Parkinson’s disease is plotted against the HLA profile of dementia.
The two HLA disease profiles were highly correlated. N = 127.
Figure 6.
Figure 6.. The HLA Class I profile of Parkinson’s disease is plotted against the HLA Class I profile of dementia.
The two HLA disease profiles were highly correlated. N = 68 alleles.
Figure 7.
Figure 7.. The HLA Class II profile of Parkinson’s disease is plotted against the HLA Class II profile of dementia.
The two HLA disease profiles were highly correlated. N = 59 alleles.
Figure 8.
Figure 8.
Diagram illustrating putative protective and susceptibility roles of HLA in disease outcomes.
See this image and copyright information in PMC

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References

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