Primer Design for Detecting Single Nucleotide Polymorphisms within the Oxytocin Receptor Gene (OXTR) among Persons with Alzheimer Disease

Abstract

Apathy, defined as a disorder of motivation with deficits in behavioral, emotional, and cognitive domains, is a prevalent behavioral symptom among persons with Alzheimer Disease (AD). Various complications have been associated with apathy, such as physical deconditioning, uncooperativeness with care, and social isolation. Little is known about the characteristics of persons with AD, including biological factors, that contribute to the presence and/or severity of apathy. Variations in the Oxytocin Receptor Gene (OXTR) are hypothesized to be candidate modifiers of apathy severity in persons with AD. OXTR is approximately 19,000 bp in length and is located on chromosome 3. A DNA variant within OXTR (rs53576) significantly predicted 19.4% of the variance in apathy severity as measured by the Apathy subscale of the Neuropsychiatric Inventory (NPI-Apathy) (F=3.379, p=.027), while controlling for cognitive status and number of Apolipoprotein E (APOE) e4 alleles in a previous study. The aims of this study were to design and successfully utilize primers and polymerase chain reaction (PCR) in order to amplify OXTR single nucleotide polymorphisms (SNPs) as a means to examine variations within OXTR that may be associated with apathy in persons with AD. Primer sets were designed to amplify seven SNPs (rs53576, rs237885, rs2254298, rs237887, rs2268493, rs2268498, and rs13316193) within OXTR and were tested using ten lab control human DNA samples. Gel electrophoresis results showed that bands migrated appropriate distances for the expected length of DNA fragments. This indicated successful DNA extraction, primer design, and amplification of all seven SNPs. Study findings may contribute to a risk profile for identifying individuals with AD most at risk for apathy based on OXTR genotype, with a long-term goal to design targeted nursing interventions to benefit these individuals