An exploratory study on CLU, CR1 and PICALM and Parkinson disease.
An exploratory study on CLU, CR1 and PICALM and Parkinson disease.
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DOI：
10.1371/journal.pone.0024211
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Gao J;Huang X;Park Y;Hollenbeck A;Chen H
最近的GWAS和随后的确认研究报告了CLU、CR 1和PICALM基因座的几个单核苷酸多态性（SNP）与迟发性阿尔茨海默病（AD）相关。帕金森病（PD）与AD有几个共同的临床和病理特征;因此，我们探讨了这些SNP是否也与PD风险相关。791名非西班牙裔白人病例和1，580名匹配的对照被纳入研究。优势比（OR）和95%置信区间（CI）从逻辑回归模型获得。在调整出生年份、性别、吸烟和咖啡因摄入量后，隐性模型（TT与CC+CT比较：OR = 0.71，95%CI：0.55-0.92，p =0.008）下，CLU基因座的rs 11136000与PD风险相关。 进一步校正PD家族史和ApoE ε4状态未改变结果。此外，我们没有发现ApoE或已知PD风险因素影响疗效的证据。然而，PD伴痴呆（OR = 0.49，95%CI：0.27-0.91）的相关性似乎强于PD不伴痴呆（OR = 0.81，95%CI：0.61-1.06）。 另外两个SNPs，来自CR 1的rs6656401和来自PICALM区域的rs3851179与PD无关（p>0.05）。我们的探索性分析表明CLU与PD相关。这一探索性发现以及痴呆在解释这一发现中的作用需要进一步研究。
Recent GWAS and subsequent confirmation studies reported several single-nucleotide polymorphisms (SNPs) at the CLU, CR1 and PICALM loci in association with late-onset Alzheimer's disease (AD). Parkinson disease (PD) shares several clinical and pathologic characteristics with AD; we therefore explored whether these SNPs were also associated with PD risk. 791 non-Hispanic Whites cases and 1,580 matched controls were included in the study. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models. rs11136000 at the CLU locus was associated with PD risk under the recessive model (comparing TT versus CC+CT: OR = 0.71, 95% CI: 0.55-0.92, p = 0.008) after adjusting for year of birth, gender, smoking, and caffeine intake. Further adjustment for family history of PD and ApoE ε4 status did not change the result. In addition, we did not find evidence for effect modification by ApoE or known PD risk factors. The association, however, appeared to be stronger for PD with dementia (OR = 0.49, 95% CI: 0.27-0.91) than for PD without dementia (OR = 0.81, 95% CI: 0.61-1.06). The two other SNPs, rs6656401 from CR1, and rs3851179 from PICALM region were not associated with PD (p>0.05). Our exploratory analysis suggests an association of CLU with PD. This exploratory finding and the role of dementia in explaining this finding needs further investigation.
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