Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.

Abstract

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA(2) activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA(2) activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA(2) activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6 x 10(-24)); CELSR2/PSRC1 on chromosome 1 (p = 3 x 10(-15)); SCARB1 on chromosome 12 (p = 1x10(-8)) and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4 x 10(-8)). All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA(2) mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA(2) activity and mass.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pgen.1000928

Publication Info

Suchindran, Sunil, David Rivedal, John R Guyton, Tom Milledge, Xiaoyi Gao, Ashlee Benjamin, Jennifer Rowell, Geoffrey S Ginsburg, et al. (2010). Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet, 6(4). p. e1000928. 10.1371/journal.pgen.1000928 Retrieved from https://hdl.handle.net/10161/13543.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Guyton

John Richard Guyton

Professor Emeritus of Medicine

Current research efforts focus on the role of niacin in clinical lipid practice. Despite the ending of a large clinical trial due to lack of benefit, niacin remains the second best lipid-modifying drug after statins. Why this trial did not replicate earlier success with niacin is a matter of great interest. Counterregulatory hormone responses may provide the answer. Another research focus is weight loss counseling in the busy clinic setting. Low glycemic dietary advice achieved average long-term weight loss of 3% (beyond 1 year) in a recently published study. One in four patients had long-term weight loss greater than 6%.

Dr. Guyton is recognized nationally as an expert in clinical management of lipid disorders and a leader in postgraduate education in this area. Both nationally and internationally, Dr. Guyton is known for his earlier work on lipid deposition in the arterial wall.

Key words: atherosclerosis, lipoproteins, statins, niacin, triglycerides, low density lipoproteins, high density lipoproteins

Rowell

Jennifer Voigt Rowell

Assistant Professor of Medicine
McCarthy

Jeanette Joan McCarthy

Adjunct Associate Professor in the Department of Family Medicine and Community Health

As a genetic epidemiologist, I spent the earlier part of my career researching the genetic underpinnings of complex diseases, both infectious and chronic. More recently, I have turned my attention to precision medicine education. As a leading educator in the field of genomic and precision medicine, I now spend my time demystifying genomics for non-technical audiences, including health care providers, patients and other stakeholders. In 2014 I helped launch the first consumer-facing magazine in this field, Genome, where I served as editor-in-chief until 2016. I teach genomic and precision medicine online through Coursera and through the Precision Medicine Academy. I also design and deliver custom workshops and courses to international audiences. My workshops and online courses are meant to increase awareness, improve genomic literacy and teach practical skills for implementing precision medicine.  I am also coauthor of the book, Precision Medicine: A Guide to Genomics in Clinical Practice (2016, McGraw Hill Education).

Visit: Precision Medicine Academy  precisionmedicineacademy.org


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.