Genetic factors predicting Lp-PLA 2 activity and their association with cardiovascular-related mortality and morbidity

Research output: Contribution to conferencePoster

Abstract

Lipoprotein-associated phospholipase A 2 (Lp-PLA 2), is a vascular-specifi c,
proinfl ammatory enzyme that is known to increase the risk of CVD events
and stroke. Chu et al. conducted a meta-analysis of genome-wide association
studies across the CHARGE consortium and JUPITER study to identify genetic
variants associated with the mass and activity of the enzyme. We sought
to replicate the fi ndings in a cohort of 7,000 Scottish Caucasian individuals in
the GoDARTS study for whom Lp-PLA 2 activity levels had been measured. We
replicate one of fi ve loci associated with Lp-PLA 2 mass and eight of nine loci
associated with Lp-PLA 2 activity, with the ninth variant showing borderline signifi
cance (p = 0.07). Notably, the variants in PLA2G7 (rs1362931, β = 3.24, P
= 4 x 10 -5) and APOC1-APOE (rs7412, β = -7.4, P = 2 x 10 -10 and rs445925, β= -5.0, P = 1.6 x 10 -6) were strongly associated with Lp-PLA 2 activity in models adjusted for BMI, age, sex and smoking status, similar to the original study. In context of Lp-PLA 2‘s role in cardiovascular health, we decided to examine the impact of these variants on related mortality and morbidity. We classifi ed statin users who were subsequently hospitalized due to an ischemic event or coronary artery disease or had the same events recorded as their cause of death, as having statin failure. We fi nd the variant in PLA2G7 is associated with this outcome, both cross-sectionally and longitudinally. In the highest quartile of Lp-PLA 2 levels homozygous carriers of the variant (T/T) had 1.7 times the hazards of having statin failure compared to homozygous carriers of the ancestral allele (p value = 0.035).
Original languageEnglish
Publication statusPublished - 18 Oct 2016
Event66th Annual Meeting of the American Society of Human Genetics - Vancouver Convention Centre, Vancouver, Canada
Duration: 18 Oct 201622 Oct 2016
http://www.ashg.org/2016meeting/ (Link to Conference website)

Conference

Conference66th Annual Meeting of the American Society of Human Genetics
Abbreviated titleASHG 2016
CountryCanada
CityVancouver
Period18/10/1622/10/16
Internet address

Keywords

  • Cardiovascular events
  • Genetic epidemiology
  • statistical modelling

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  • Cite this

    Siddiqui, M. K., Kennedy, G., Carr, F., Doney, A., & Palmer, C. N. A. (2016). Genetic factors predicting Lp-PLA 2 activity and their association with cardiovascular-related mortality and morbidity. Poster session presented at 66th Annual Meeting of the American Society of Human Genetics, Vancouver, Canada.