Association of a regulatory anti-oxidant and drug-metabolising gene with multi-morbidity and adverse drug reactions in older adults

Greg Scutt, Andrew Overall, Prijay Bakrania, Eliseveta Krasteva, Nikesh Parekh, Khalid Ali, Graham Davies, Chakravarthi Rajkumar

Research output: Contribution to conferenceOther

Abstract

Introduction Multimorbidity and adverse drug reactions (ADR) are problems associated with ageing populations. Exploring underlying genetic predispositions might help to risk-stratify patients for early intervention. The nuclear factor erythroid 2-like 2 (Nrf2) protein regulates antioxidant and de-toxifying effectors in the cell. Nrf2 expression declines with age, potentially increasing vulnerability to multimorbidity and ADR. We hypothesise that single nucleotide polymorphisms (SNPs) at 3 loci in the Nrf2 gene are associated with multimorbidity and ADR in older adults.
Methods One-hundred and twenty-seven patients were recruited from a sub-population of the PRIME study (a multicentre prospective cohort study that followed older adults over 8-weeks post-discharge to determine ADR status). Donated genetic material was sequenced to determine genotype at 3 loci: rs6721961, rs35652124 and rs6706649 and then analysed for association with ADR (Naranjo Algorithm), multimorbidity (3 conditions defined by the Charlson Index (CI)).
Results One-hundred and twelve patients (mean age 76.6±7.3 years, 55.4% female) were successfully genotyped. In patients aged 65-79, those with the rs35652124 A allele showed increased odds of having 3 co-morbidities (OR 9.03 95%CI 1.16-70.2, p=0.0127). Individuals with the CGG haplotype in this age-group showed reduced odds of multimorbidity (OR 0.11, 95% CI 0.01-0.86, p=0.001). No association between Nrf2 geno/haplotype and ADR was identified.
Conclusions Polymorphisms in the Nrf2 gene are associated with multimorbidity, but not ADR, in older adults.
Original languageEnglish
Publication statusPublished - 2018

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