Objective: To investigate whether cigarette smoking influences the relationship between S1647T variants and risk of PD in the Singapore population.

Background: Case-control studies in southern China have reported LRRK2 S1647T to be a risk variant for PD in Han Chinese, with a higher frequency of A allele detected in PD patients. Recent analyses of case-control studies in France and California have also elicited an inverse correlation between smoking and PD, and therefore it is worthwhile to evaluate the relationship between S1647T variants and smoking.

Methods: A total of 2,000 subjects (1,143 males and 857 females) were recruited from the two campuses of the National Neuroscience Institute and Singapore General Hospital. All 1,000 subjects diagnosed with PD (600 males and 400 females) and 1,000 controls (543 males and 457 females) were administered a screening questionnaire which included demographics, medical history and smoking history, among others. Genomic DNA was extracted from venous blood. S1647T variants were identified by Sanger sequencing.

Results: Smoking pack years was not significantly associated with PD diagnosis. Presence of A allele in S1647T was significantly associated with PD diagnosis (p=.040, OR=1.23), adjusted for age, gender and race. Heterozygous (TA) variant was identified in 49.3% of cases and 44.2% of controls, while homozygous (AA) in 13.8% of the cases and 14.7% of the controls. Compared to wildtype, the heterozygous variant is borderline significantly associated with PD (p=.0497, OR=1.216) adjusted for age, gender and smoking. Subgroup analysis shows this association is more prominent in Chinese (p=.034, OR=1.23) adjusted for age, gender and smoking.

Conclusions: The cohort lacked significance in the association of smoking pack years and PD diagnosis. However, the presence of A allele in S1647T seems to be significantly associated with PD diagnosis, especially in the Chinese subgroup.

References: Lin, C. H., Wu, R. M., Tai, C. H., Chen, M. L., & Hu, F. C. (2011). Lrrk2 S1647T and BDNF V66M interact with environmental factors to increase risk of Parkinson’s disease. Parkinsonism & related disorders, 17(2), 84-88. Peeraully, T., & Tan, E. K. (2012). Genetic variants in sporadic Parkinson’s disease: East vs West. Parkinsonism & related disorders, 18, S63-S65. Tan, E. K., & Schapira, A. H. (2011). New LRRK2 variants identified in Parkinson’s disease. European journal of neurology, 18(3), 369-370. Wu, Y. R., Chang, K. H., Chang, W. T., Hsiao, Y. C., Hsu, H. C., Jiang, P. R., … & Hu, F. J. (2013). Genetic variants of LRRK2 in Taiwanese Parkinson’s disease. PloS one, 8(12), e82001. Zheng, Y., Pei, Z., Liu, Y., Zhou, H., Xian, W., Fang, Y., … & Wu, Q. (2015). Cognitive impairments in LRRK2-related Parkinson’s disease: A study in Chinese individuals. Behavioural neurology, 2015.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-the-relationship-between-leucine-rich-repeat-kinase-2-lrrk2-s1647t-variants-and-smoking-with-risk-of-parkinsons-disease-in-the-singapore-population/