Genetic association of the gene encoding RPGRIP1L with susceptibility to vascular dementia |
| |
Authors: | Woo Jiyoung Lee Chaeyoung |
| |
Institution: | School of Systems Biomedical Science, Soongsil University, Seoul 156-743, South Korea. |
| |
Abstract: | 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(-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<7.6×10(-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. |
| |
Keywords: | 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 RPGRIP1L retinitis pigmentosa GTPase regulator-interacting protein 1-like SNP single nucleotide polymorphism VaD vascular dementia |
本文献已被 ScienceDirect PubMed 等数据库收录! |