BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

Free Newsletters
My Subscriptions

News by Subject
News by Disease
News by Date
Search News
Post Your News

Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Pharm Country
  Bio NC
  Southern Pharm
  BioCanada East
  C2C Services & Suppliers™


Company Profiles

Research Store

Research Events
Post an Event
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Molecular Biology - Pathology - Public Health and Epidemiology

Functional Analysis of Two PLA2G2A Variants Associated with Secretory Phospholipase A2-IIA Levels
Published: Tuesday, July 17, 2012
Author: Holly J. Exeter et al.

by Holly J. Exeter, Lasse Folkersen, Jutta Palmen, Anders Franco-Cereceda, Jackie A. Cooper, Anastasia Z. Kalea, Ferdinand van’t Hooft, Per Eriksson, Steve E. Humphries, Philippa J. Talmud


Secretory phospholipase A2 group IIA (sPLA2-IIA) has been identified as a biomarker of atherosclerosis in observational and animal studies. The protein is encoded by the PLA2G2A gene and the aim of this study was to test the functionality of two PLA2G2A non-coding SNPs, rs11573156 C>G and rs3767221 T>G where the rare alleles have been previously associated with higher and lower sPLA2-IIA levels respectively.

Methodology/Principal Findings

Luciferase assays, electrophoretic mobility shift assays (EMSA), and RNA expression by RT-PCR were used to examine allelic differences. For rs3767221 the G allele showed ~55% lower luciferase activity compared to the T allele (T?=?62.1 (95% CI 59.1 to 65.1) G?=?27.8 (95% CI 25.0 to 30.6), p?=?1.22×10-35, and stronger EMSA binding of a nuclear protein compared to the T-allele. For rs11573156 C >G there were no luciferase or EMSA allelic differences seen. In lymphocyte cell RNA, from individuals of known rs11573156 genotype, there was no allelic RNA expression difference for exons 5 and 6, but G allele carriers (n?=?7) showed a trend to lower exon 1–2 expression compared to CC individuals. To take this further, in the ASAP study (n?=?223), an rs11573156 proxy (r2?=?0.91) showed ~25% higher liver expression of PLA2G2A (1.67×10-17) associated with the G allele. However, considering exon specific expression, the association was greatly reduced for exon 2 (4.5×10-5) compared to exons 3–6 (10-10 to 10-20), suggesting rs11573156 G allele-specific exon 2 skipping.


Both SNPs are functional and provide useful tools for Mendelian Randomisation to determine whether the relationship between sPLA2-IIA and coronary heart disease is causal.