LRRK2 gene in individuals from the Xinjiang region of China, and to explore the associations between LRRK2 gene single nucleotide mutations and susceptibility to PD in the Uyghur and Han populations

In recent genome-wide association studies (GWAS), 11 risk loci were identified in patients with familial and sporadic Parkinson's disease (PD) in different populations. The LRRK2 gene was found to be a mutation hot spot in European and Asian populations. The aim of the present study was to investigate the incidence of G2019S and R1441C mutations in the LRRK2 gene in individuals from the Xinjiang region of China, and to explore the associations between LRRK2 gene single nucleotide mutations and susceptibility to PD in the Uyghur and Han populations of Xinjiang. A case-control study was conducted with a group of 312 patients with PD, including 130 Uyghur and 182 Han individuals. The control group comprised 359 subjects, including 179 Uyghur and 180 Han individuals. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods were used to detect the G2019S and R1441C mutations in the LRRK2 gene in the Uyghur and Han populations. No known mutations or new hybrids were found. Thus, there was no evidence that Uyghur and Han patients with PD possess the G2019S or R1441C mutations of the LRRK2 gene. This does not exclude the possibility of the presence other LRRK2 gene mutations that are associated with PD in the Uyghur and Han populations. In the future, the association of the LRRK2 gene with PD development in different regions and populations requires further study, in addition to the regulatory effects of the G2019S and R1441C mutations on gene expression. Introduction Parkinson's disease (PD) is a common degenerative disease of the central nervous system in the elderly, which is primarily associated with environmental and genetic factors. There are a number of genes that have been established to be associated with PD, which include LRRK2. Mutations of LRRK2 are considered to be the most prevalent in the pathogenesis of PD; in studies of North American and European PD patients, 5% had a mutation of LRRK2 and a family history of PD, while 1-2% had sporadic PD (1-4). The LRRK2 gene is the causative gene of the autosomal dominant hereditary type 8 PD (5,6). It is composed of five structural domains, namely, the ankyrin repeat (ANK), leucine-rich repeat (LRR), Ras of complex proteins (Roc) C-terminal of Roc (COR), mitogen activated kinase kinase kinase (MAPKKK) and WD40 regions (7-9). Major mutations of LRRK2 include R1441C, R1441G, R1441H, R1514Q, Y1699C, G2019S, I2020T, I2012T and G2385R (10-12). Mutations of LRRK2 have been associated with a number of diseases, in particular with familial PD and sporadic PD, and the G2019S mutation is one of the most common mutations in PD (13). Clear racial and regional differences exist in the incidence of PD. Xinjiang is an autonomous region located in Central Asia, which has two predominant populations with different genetic backgrounds, namely, the Uyghur and Han populations. The current case-control study selected PD patients and healthy individuals from the Uyghur and Han populations of the Xinjiang region for the analysis of LRRK2 gene mutations. To the best of our knowledge, this is the first time that the association between the G2019S and R1441C mutations of the LRRK2 gene and PD susceptibility has been investigated in different ethnicities and regions. Subjects and methods Diagnostic criteria and study subjects. From June 2010 to April 2013, 312 patients with PD (all sporadic) visiting the specialist neurology clinic of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, China) were enrolled in the study. The diagnosis was in line with the UK Brain Bank diagnostic criteria for PD. Cerebrovascular disease, encephalitis, trauma, drug-induced Parkinson's syndrome, Parkinson's plus syndrome and other severe systemic diseases were excluded. The control group consisted of 359 volunteers Association between Parkinson's disease and G2019S and R1441C mutations of the LRRK2 gene XIAO-XIA LI1*, QIN LIAO2*, HUAN XIA2* and XIN-LING YANG2 1Internal Medicine-Neurology, Leshan People's Hospital, Leshan, Sichuan 614000; 2Cadre's Wards, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China Received March 13, 2014; Accepted November 6, 2014 DOI: 10.3892/etm.2015.2659 Correspondence to: Dr Xin-Ling Yang, Cadre's Wards, The Affiliated Tumor Hospital of Xinjiang Medical University, 137 Liyushan Road, Urumqi, Xinjiang 830054, P.R. China E-mail: [email protected] *Contributed equally