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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Drug-Related Side Effects and Adverse Reactions
Oxidants
Comorbidity
Morbidity
Pharmaceutical Preparations
Genes
Haplotypes
Genetic Predisposition to Disease
Population
Multicenter Studies
Single Nucleotide Polymorphism
Cohort Studies
Age Groups
Antioxidants
Alleles
Genotype
Prospective Studies
Proteins

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Scutt, Greg ; Overall, Andrew ; Bakrania, Prijay ; Krasteva, Eliseveta ; Parekh, Nikesh ; Ali, Khalid ; Davies, Graham ; Rajkumar, Chakravarthi. / Association of a regulatory anti-oxidant and drug-metabolising gene with multi-morbidity and adverse drug reactions in older adults.
@conference{076379b1a783400986da76a280a5444d,
title = "Association of a regulatory anti-oxidant and drug-metabolising gene with multi-morbidity and adverse drug reactions in older adults",
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.",
author = "Greg Scutt and Andrew Overall and Prijay Bakrania and Eliseveta Krasteva and Nikesh Parekh and Khalid Ali and Graham Davies and Chakravarthi Rajkumar",
year = "2018",
language = "English",

}

Association of a regulatory anti-oxidant and drug-metabolising gene with multi-morbidity and adverse drug reactions in older adults. / Scutt, Greg; Overall, Andrew; Bakrania, Prijay; Krasteva, Eliseveta; Parekh, Nikesh; Ali, Khalid; Davies, Graham; Rajkumar, Chakravarthi.

2018.

Research output: Contribution to conferenceOther

TY - CONF

T1 - Association of a regulatory anti-oxidant and drug-metabolising gene with multi-morbidity and adverse drug reactions in older adults

AU - Scutt, Greg

AU - Overall, Andrew

AU - Bakrania, Prijay

AU - Krasteva, Eliseveta

AU - Parekh, Nikesh

AU - Ali, Khalid

AU - Davies, Graham

AU - Rajkumar, Chakravarthi

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

M3 - Other

ER -