Ong Yi-Lin, Deng Xiao, Li Hui-Hua, Narasimhalu K, Chan Ling-Ling, Prakash Kumar M, Au Wing-Lok, Ratnagopal Pavanni, Tan Louis C S, Tan Eng-King
Duke-NUS Medical School, Singapore.
National Neuroscience Institute, Singapore.
Lancet Reg Health West Pac. 2023 Sep 4;40:100877. doi: 10.1016/j.lanwpc.2023.100877. eCollection 2023 Nov.
Caffeine intake reduces risk of Parkinson's disease (PD), but the interaction with genes is unclear. The interaction of caffeine with genetic variants in those at high PD risk has healthcare importance. We investigate interactions of caffeine intake with risk variants found in Asians, and determine PD risk estimates in caffeine-drinkers carrying these variants.
PD patients and controls without neurological disorders were included. Caffeine intake was assessed using a validated evaluation tool. Leucine rich repeat kinase 2 (LRRK2) risk variants were genotyped. Statistical analysis was conducted with logistic regression models. Gene-caffeine interactions were quantified using attributable proportion (AP) due to interaction (positive interaction defined as AP >0).
5100 subjects were screened and 4488 subjects (1790 PD, 2698 controls) with genetic data of at least one LRRK2 variant were included. Risk-variant-carriers who were non-caffeine-drinkers had increased PD odds compared to wildtype carriers who were caffeine-drinkers for G2385R [OR 8.6 (2.6-28.1) p < 0.001; AP = 0.71], R1628P [OR 4.6 (1.6-12.8) p = 0.004; AP = 0.50] and S1647T [OR 4.0 (2.0-8.1) p < 0.001; AP = 0.55] variants.
Caffeine intake interacts with LRRK2 risk variants across three different groups of gene carriers. Asymptomatic risk-variant-carriers who are non-caffeine-drinkers have four to eight times greater PD risk compared to wildtype-caffeine-drinkers. Lifestyle modifications to mitigate PD risk in asymptomatic healthy risk variant carriers have potential roles in our Asian cohort.
This study was supported by the National Medical Research Council (STaR and PD OF LCG 000207 grants) and Duke-NUS Medical School.
摄入咖啡因可降低帕金森病（PD）风险，但与基因的相互作用尚不清楚。咖啡因与高PD风险人群基因变异的相互作用具有重要的医疗意义。我们研究了咖啡因摄入与亚洲人群中发现的风险变异之间的相互作用，并确定携带这些变异的咖啡因饮用者的PD风险估计值。
纳入PD患者和无神经系统疾病的对照。使用经过验证的评估工具评估咖啡因摄入量。对富含亮氨酸重复激酶2（LRRK2）的风险变异进行基因分型。采用逻辑回归模型进行统计分析。使用因相互作用产生的归因比例（AP）对基因-咖啡因相互作用进行量化（正相互作用定义为AP>0）。
共筛查了5100名受试者，纳入了4488名至少有一个LRRK2变异基因数据的受试者（1790名PD患者，2698名对照）。对于G2385R变异，非咖啡因饮用者且携带风险变异的人群与饮用咖啡因的野生型携带者相比，PD患病几率增加[比值比（OR）8.6（2.6 - 28.1），p < 0.001；AP = 0.71]；对于R1628P变异，OR为4.6（1.6 - 12.8），p = 0.00�；AP = 0.50]；对于S1647T变异，OR为4.0（2.0 - 8.1），p < 0.001；AP = 0.55]。
咖啡因摄入与三组不同基因携带者中的LRRK2风险变异存在相互作用。与饮用咖啡因的野生型携带者相比，不饮用咖啡因的无症状风险变异携带者患PD的风险高出四至八倍。在我们的亚洲队列中，通过生活方式改变来降低无症状健康风险变异携带者的PD风险具有潜在作用。
本研究由国家医学研究理事会（STaR和PD OF LCG 000207资助）以及杜克 - 新加坡国立大学医学院资助。
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