The Effect of TOMM40 Gene Variants and Their Correlation with ApoE Genotype on the Pathogenesis of Alzheimer's Disease in Perimenopausal Women

The higher incidence of Alzheimer’s disease (AD) in women raises the question of gender differences in the aging process, as there are twice as many female AD patients compared to males.  In our gender specific AD study, we confirmed ApoE as the most important risk factor for AD without explaining the association with the disease in the majority of the cases, as the ApoE risk allele was not found in the most patients.  TOMM40 is a gene adjacent to ApoE gene which could be in linkage disequilibrium with ApoE and its variants could cause the the high association of ApoE with the disease. Certain variants in TOMM40 gene may confer risk for Alzheimer’s disease, specifically in perimenopausal women. We screened the coding region of TOMM40 gene in a cohort 0f 700 AD, MCI, and healthy controls from Texas Alzheimer’s Research and Care Consortium (TARCC) We amplified each exon through Polymerase Chain reaction (PCR) and sequenced each amplimer using fluorescent method. The sequencing assays were run on an ABI 3730 DNA Analyzer.  The sequences were ultimately analyzed using Sequencher software. We will use the sequencing results for identification of additional risk factors and use all the identified variants to build haplotypes using the haploview software. Our goal is to determine the risk factors of AD, specifically in women to provide early detection and intervention to delay and ultimately prevent AD by treating the risk factors at the early stages.