The Research On The Association Between GBA Gene Mutations And Parkinson's Disease In Chinese Population

Background:Parkinson's disease (PD) is a common neurodegenerative disease, especially in senior group.It is characterized by resting tremor, rigidity, bradykinesia, and postural instability. It is widely accepted that environmental, hereditary factors and progress of aging all have essential influences on the mechanism of onset of PD. Gaucher disease is an inherited autosomal recessive metabolic defect due to a deficiency in the lysosomal enzymeβ-glucocerebrosidase, which leads to an accumulation of glucocerebroside in the body, predominantly in the liver, spleen, and bone marrow. Clinically, Gaucher disease is a multisystemic disease with variable manifestations, characterized by hepatosplenomegaly and cytopenia. Recent researches discovered that GBA gene mutations may increase the risk for Parkinson's disease, and may differentiate between patient subgroups. The research on the association between GBA gene mutation and Parkinson's disease has become current hot spots. In a study of Ashkenazi Jews, N370S was found in 78% of GD patients. In non-Jewish populations, the most common mutation was L444P (36%), followed by N370S (29%). Mutation analysis of Chinese GD patients has reported three common mutations:L444P, F213I, R353W.Objective:To investigate the possible association between GBA gene mutations and PD in Chinese population.Method:We screened the frequency of GBA gene L444P, F213I, R353W and N370S mutations in 402 sporadic PD patients and 413 unrelated healthy controls from mainland China. We utilized restricted fragments length polymorphism and DNA direct sequencing methods to identify genotype of these four variants. To assess the possible role of GBA gene L444P mutation in PD in Chinese population and other populations, we conducted a meta-analysis on the topic. Result:Among the 402 Chinese PD patients, we found eleven patients (2.74%) who carried a heterozygous mutant GBA allele. The eleven heterozygotes have the L444P mutation. No heterozygotes were found among the 413 age-and sex-matched controls. We compared the frequency of heterozygotes for the GBA gene L444P mutation among PD patients (11/402) and the control group (0/413) by means of the chi-square test. The difference was statistically significant (χ2=11.46, P=0.0007, OR=24.29; confidence interval=95%,1.43-413.63). The results of Meta analysis:In the Chinese population, the GBA gene L444P mutation was detected at a significantly higher frequency among PD patients, when compared to the control group:Z=3.83, p=0.0001, OR=8.42, confidence interval=95%,2.83-25.06; The difference between the frequency of GBA mutations in PD patients and the frequency in control group was non-significant in the Ashkenazi Jewish population: Z=1.84, p=0.07, OR=4.94, confidence interval=95%,0.90-27.08; In the non-Jewish populations, the difference was obviously significant:Z=5.76, p<0.00001,OR=8.82, confidence interval=95%,4.21-18.48.Conclusion:1. GBA gene L444P mutation appears to be a risk factor for PD in Chinese population.2. GBA gene N370S, F213I and R353W mutations may be not risk factors for PD in mainland China.