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      HLA-DRB1 Alleles Are Associated with the Susceptibility to Sporadic Parkinson’s Disease in Chinese Han Population

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          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 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.

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          Most cited references64

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          Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

          Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
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            A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.

            The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
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              Parkinson's disease. Second of two parts.

              At no time in the past have the basic and clinical sciences applied to Parkinson's disease been so active. Experimental therapies under study at present promise to improve on the limitations of existing treatments. Future progress in understanding the causation and pathogenesis of the disorder will permit the development of new treatments that will slow, halt, or even reverse the currently inexorable progressive course of Parkinson's disease.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                6 November 2012
                : 7
                : 11
                : e48594
                Affiliations
                [1 ]Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
                [2 ]Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
                [3 ]Department of Neurology, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China
                [4 ]Department of Neurology, Department of Neurology, Red-Cross Hospital in Guangzhou, Guangzhou, People’s Republic of China
                [5 ]Department of Neurology, HeYuan City Hospital, Guangdong, People’s Republic of China
                [6 ]Department of Neurology, Yuebei People's Hospital of Shantou University Medical College, Guangdong, People’s Republic of China
                [7 ]Department of Neurology, The First People’s Hospital of Shaoguan, Guangdong, People’s Republic of China
                [8 ]Department of Neurology, The First Affiliated Hospital of NanChang University, NanChang, People’s Republic of China
                [9 ]Department of Tissue Typing Center, Nanfang Hospital of Southern Medical University, Guangzhou, People’s Republic of China
                National Institutes of Health, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CS ZL PX. Performed the experiments: CS LW FL YL LX. Analyzed the data: CS. Contributed reagents/materials/analysis tools: JL FZ PK RX. Wrote the paper: CS PX.

                Article
                PONE-D-12-13009
                10.1371/journal.pone.0048594
                3490875
                23139797
                f9359c41-954b-4baa-b40e-52b625a97616
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 April 2012
                : 26 September 2012
                Page count
                Pages: 9
                Funding
                The trial costs were supported by research grants from the National High Technology Research and Development Program of China (grant 2007AA022460) and the State Key Development Program for Basic Research of China (grant 2011CB510000). The data collection and analysis were supported by research grants from the National Natural Science Foundation of China (grant 81071032 and 81271428). The preparation of the manuscript and publication fees were supported by research grants from the Guangzhou Foundation for scientific and technological project, China (grant 2012J4300061) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (grant 20100171110056). These funders had no role in study design, decision to publish.
                Categories
                Research Article
                Biology
                Biochemistry
                Proteins
                Major Histocompatibility Antigens
                Genetics
                Population Genetics
                Genetic Polymorphism
                Genetics of Disease
                Immunology
                Major Histocompatibility Complex
                Neuroscience
                Population Biology
                Epidemiology
                Genetic Epidemiology
                Population Genetics
                Genetic Polymorphism
                Medicine
                Clinical Immunology
                Major Histocompatibility Complex
                Epidemiology
                Genetic Epidemiology
                Neurology
                Parkinson Disease

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                Uncategorized

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