Genetic association of the gene encoding RPGRIP1L with susceptibility to vascular dementia

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• 作者：Jiyoung Woo ; Chaeyoung Lee ; ^{clee@ssu.ac.kr}
• 关键词：AD ; Alzheimer's disease ; ALT ; alanine aminotransferase ; AST ; aspartate aminotransferase ; BP ; blood pressure ; GWAS ; genome-wide association study ; KARE ; Korean Association REsource ; LD ; linkage disequilibrium ; OR ; odds ratio ; PCR ; polymerase chain reaction
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：10 May, 2012
• 卷：499
• 期：1
• 页码：160-162
• 文件大小：142 K

摘要

A previous genome-wide association study (GWAS) failed to discover any nucleotide sequence variant associated with susceptibility to vascular dementia (VaD) and remained a problem of false negatives produced by a low statistical power. The current study was conducted to identify such potential false negatives and to provide comprehensive evidence for the most plausible predisposing genetic factor using large-scale Korean cohorts. We identified the gene encoding retinitis pigmentosa GTPase regulator-interacting protein 1-like (RPGRIP1L) with multiple nucleotide variants associated with susceptibility to VaD by a modest significant threshold (P < 10^鈭?#xA0;4). Genetic associations were intensively examined with its sequence variants using 207 VaD patients and 207 age- and gender-matched control subjects. Genetic association analysis with dense variants in the region associated with VaD revealed 3 variants (P < 0.0017) in strong linkage. Further analysis with VaD-related phenotypes using Korean Association REsource (KARE) cohort data showed that the region of the gene was associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood pressure (BP) (P < 7.6 脳 10^鈭?#xA0;4). The current study provided the first evidence of the association between RPGRIP1L gene and susceptibility of VaD. Functional studies are needed to understand underlying biological mechanism of the genetic association.