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PLoS ONE:研究揭示咖啡如何防止帕金森氏症

来源:生物谷 2014-07-16 09:29

2014年7月16日讯 /生物谷BIOON/--近日,瑞典林雪平大学研究人员发现的一个特定的遗传变异可防止帕金森氏症,特别是对那些喝大量咖啡的人来说。

这项研究发表在科学期刊PLOS One上。遗传和环境因素相互交互导致疾病的出现,因此研究往往侧重于查明基因和环境暴露疾病风险增加的影响。但研究指出也有遗传变异--突变和某些环境因素能预防某些疾病的出现。

神经变性疾病如帕金森氏症有一个复杂的背景,其中遗传因素和环境暴露因素共同参与其中。近日,一项研究确定了谷氨酸受体 (glutamate receptor)基因GRIN2A的一个变异可作为对帕金森氏症的保护性因素。GRIN2A基因相应的蛋白被认为在神经退行性疾病中发挥了作用。

来自瑞典的帕金森氏症患者流行病学研究考察了先前已知的保护性因素的组合--咖啡因和GRIN2A遗传变异。研究结果表明,这种组合对帕金森氏症发生风险的影响是显著降低的。

该研究给出了增加咖啡因摄入量对帕金森发展有保护作用的一个分子解释,咖啡因与一种调节钙流入细胞的多巴胺受体结合,而多巴胺受体可以调节钙质流入细胞。多巴胺是机体奖赏系统的一部分,由于咖啡因与它的相互作用,推测咖啡对某些遗传变异个体的“奖励”程度是不一样的,因此某些遗传突变的个体喝一杯咖啡后并不会得到所谓的“奖赏”。新发表的研究表明,GRIN2A遗传变异是帕金森氏症遗传易感性的一种影响因素。(生物谷Bioon.com)

Caffeine Interaction with Glutamate Receptor Gene GRIN2A: Parkinson's Disease in Swedish Population

Naomi Yamada-Fowler, Mats Fredrikson och Peter Sderkvist

A complex interplay between genetic and environmental factors is thought to be involved in the etiology of Parkinson's disease (PD). A recent genome-wide association and interaction study (GWAIS) identified GRIN2A, which encodes an NMDA-glutamate-receptor subunit involved in brain's excitatory neurotransmission, as a PD genetic modifier in inverse association with caffeine intake. Here in, we attempted to replicate the reported association of a single nucleotide polymorphism, GRIN2A_rs4998386, and its interaction with caffeine intake with PD in patient-control study in an ethnically homogenous population in southeastern Sweden, as consistent and independent genetic association studies are the gold standard for the validation of genome-wide association studies. All the subjects (193 sporadic PD patients and 377 controls) were genotyped, and the caffeine intake data was obtained by questionnaire. We observed an association between rs4998386 and PD with odds ratio (OR) of 0.61, 95% confidence intervals (CI) of 0.39–0.96, p = 0.03, under a model excluding rare TT allele. There was also a strong significance in joint effects of gene and caffeine on PD risk (TC heavy caffeine vs. CC light caffeine: OR = 0.38, 95%CI = [0.20–0.70], p = 0.002) and gene-caffeine interaction (OR = 0.998, 95%CI = [0.991–0.999], p<0.001). Overall, our results are in support of the findings of the GWAIS and provided additional evidence indicating PD protective effects of coffee drinking/caffeine intake as well as the interaction with glutamate receptor genotypes.

 

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