Polymorphisms in immune/inflammatory cytokine genes are related to Parkinson's disease with cognitive impairment in the Han Chinese population

Abstract

Increasing evidence suggests that immune mediated inflammation contributes to the pathogenesis of Parkinson's disease (PD). However, whether genetic variants of genes coding for inflammatory cytokines influence the risk of cognitive impairment in PD is still unknown. In the present study, we examined whether interleukin-10 (IL-10, 1082G/A), interleukin-17A (IL-17A) rs8193036, rs2275913 and interferon-γ (IFN-γ) polymorphisms were associated with the risk of cognitive impairment in PD. The four gene polymorphisms were analyzed in 302 PD patients and results were compared to those obtained from 294 age- and gender-matched healthy controls (HC) enrolled from the Han Chinese population. PD patients were divided into two subgroups on the basis of mini mental state examination (MMSE) score: PD with cognitive impairment (MMSE scores < 26) and PD without cognitive impairment (MMSE scores ≥ 26). There was no significant difference in the distributions of genotype or allele between PD and control groups in the total population. However, the distribution of the rs8193036 (CC genotype, C allele) in PD individuals with an MMSE score < 26 was significantly increased when compared to PD patients with an MMSE score ≥ 26 (CC genotype: p = 0.044; C allele: p = 0.038). Also, there were significant differences in genotype and frequencies of the 1082G/A allele between PD cases with an MMSE score < 26 and controls (genotype p = 0.021; allele p = 0.024). Logistic regression analysis showed that the 1082G/A (AA) genotype decreased (Odds ratio = 0.440, p = 0.042), while the rs8193036 (CC) genotype increased the risk of cognitive impairment in PD (OR = 1.838, p = 0.048). Based on our study, polymorphisms in immune/inflammatory-related genes such as IL-17A rs8193036 and IL-10 1082G/A might be correlated with the risk of PD with cognitive impairment in the Han Chinese population.

Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease (AD). In addition to movement disorders, cognition dysfunction also seriously affects the lives of PD patients. The potential causes of PD remain elusive but studies have revealed that inflammatory processes play a vital role in the pathogenesis [22]. The impairment of inflammatory processes affects the functions of the central nervous system (CNS), among which cognition dysfunction is typical [10], [18]. Recent prospective and cross-sectional studies of Alzheimer's and vascular dementia have suggested that certain cytokines are related to cognitive impairment in these patients. For example, homozygosity for the A allele of the interleukin-10 (IL-10) 1082G/A polymorphism promotes a higher risk of AD and cognitive impairment [3], whereas the interferon-γ (IFN-γ; T874A in intron 1) genotype is involved in vascular cognitive impairment via control of IFN-γ production [24]. Of special importance in PD, where widespread cognitive impairment is extremely common [1], is the established relation between cytokines and the pathogenesis of the disease, raising the possibility that inflammatory cytokines may also play a pivotal role in PD with cognitive impairment [19]. To date however, few studies have addressed the association between inflammation-related gene polymorphisms and cognitive impairment in PD, due to the small number of patients with Parkinson's disease with dementia (PDD).

Moreover, inflammation-related genes including IL-10 1082G/A and IFN-γ T874A have been studied in the PD population [5], [14], [20], [21]. Interleukin-17A (IL17A) plays a key role in host defense against infection and development of inflammatory diseases [7], [8], [12], [15]. The two IL-17A single-nucleotide polymorphisms (SNPs) (rs8193036 and rs2275913) were associated with susceptibility to inflammatory diseases such as rheumatoid arthritis (rs2275913, risk GG allele, Norway and New Zealand) [23], paediatric asthma (rs8193036, risk CC genotype, Taiwan) [28] and ulcerative colitis (rs2275913, risk A allele, Japan) [2]. Until now, the genotype and allele distributions of the IL-17A rs8193036 and IL-17A rs2275913 polymorphisms in the PD population or PD with cognitive impairment have not been reported.

Whether IL-10 1082G/A, IL-17A rs8193036, IL-17A rs2275913 and IFN-γ T874A polymorphisms related to cognitive impairment is specific to PD is unknown. This study was undertaken to test the hypothesis that these gene polymorphisms can predict risk of PD with cognitive impairment, representing the most important risk phenotypes in the Han Chinese population.