Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55095, USA.
Parkinsonism Relat Disord. 2011 Dec;17(10):730-6. doi: 10.1016/j.parkreldis.2011.07.001. Epub 2011 Aug 3.
Polymorphisms in SNCA, MAPT and LRRK2 genes have recently been confirmed as risk factors for Parkinson's disease (PD), although with small individual attributable risk. Here we investigated the association of PD with interactions between variants of these genes.
As part of a previous study of PD susceptibility genes 119 SNCA, MAPT, and LRRK2 haplotype tagging single nucleotide polymorphisms (SNPs) and two variable number tandem repeats (VNTRs) were genotyped in 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Twenty-six of these SNPs were selected for SNP-SNP (or SNP-VNTR or VNTR-VNTR) interaction analysis (256 interaction pairs). Case-control analyses were performed to study association of pairwise SNP interactions with PD susceptibility.
Out of the 256 interaction pairs investigated, 10 had uncorrected p-values <0.05. These represented six SNCA-LRRK2 pairs, three SNCA-MAPT pairs, and one MAPT-LRRK2 pair. However, none of these pairwise interactions were significant after correction for multiple testing. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not reveal any significant interactions after accounting for multiple testing.
This study provides no statistically significant evidence of gene-gene interaction effects for the three confirmed genetic susceptibility loci for PD. However, this does not exclude the possibility that other genomic loci or environmental risk factors interact with these genes.
SNCA、MAPT 和 LRRK2 基因中的多态性最近被证实是帕金森病（PD）的风险因素，尽管个体归因风险较小。在这里，我们研究了这些基因变异之间的相互作用与 PD 的关联。
作为 PD 易感性基因研究的一部分，我们对来自美国中西部的 1098 例 PD 病例和 1098 例匹配对照进行了 119 个 SNCA、MAPT 和 LRRK2 单倍型标签单核苷酸多态性（SNP）和两个可变数串联重复（VNTR）的基因分型。选择了其中的 26 个 SNP 进行 SNP-SNP（或 SNP-VNTR 或 VNTR-VNTR）相互作用分析（256 个相互作用对）。进行病例对照分析以研究成对 SNP 相互作用与 PD 易感性的关联。
在所研究的 256 个相互作用对中，有 10 对的未校正 p 值<0.05。这代表了六个 SNCA-LRRK2 对、三个 SNCA-MAPT 对和一个 MAPT-LRRK2 对。然而，在进行多次检验校正后，这些成对相互作用均无统计学意义。在根据对照类型（同胞或无关）、性别或病例发病年龄定义的亚组中进行的二次分析，在考虑到多次检验后也没有发现任何显著的相互作用。
这项研究没有提供三个已确认的 PD 遗传易感性基因座的基因-基因相互作用效应的统计学显著证据。然而，这并不排除其他基因组区域或环境风险因素与这些基因相互作用的可能性。
