The Association of a Single Nucleotide Polymorphism in the Kelch-Like ECH- Associated Protein 1 Gene with Adverse Drug Reactions, Multimorbidity, and Frailty in Older People

Abstract

The risk of adverse drug reactions (ADRs), multimorbidity and frailty is associated with oxidative stress theory in the elderly population. Keap1 has a potential role against the damage caused by oxidative stress in cells and it is involved in regulating drug metabolism enzymes. This study aimed to investigate the impact of certain genetic polymorphisms in Keap1 among the elderly in the prediction of ADR risk, morbidity and frailty. Specifically, we tested the genetic single-nucleotide polymorphisms (SNPs) at rs1048290 in the Keap1 gene by using donated cheek swab samples obtained from the PRIME study (a multicentre prospective cohort study that followed older patients 8- weeks post-discharge). This can help to understand the genetic variation in response to certain medicines and is important for building a model to predict ADR risk, morbidity and frailty based on individuals’ genetic data. The participants were aged 66 and over and underwent eight-week post-discharge to determine any ADRs according to the Naranjo Algorithm. The data were analysed by using the PCR technique and collected for genotyping. We found a significant association between the B allele at rs1098290 in Keap1 and ADR development among the participants (p-value < 0.05). Moreover, the link between impairment in the daily physical activities based on the Barthel index and the presence of the B allele at rs1048290 in Keap1 was determined (p-value < 0.05). However, no correlation between this allele and frailty and comorbidities were determined among the participants.