title: A previously unreported impact of a PLA2G7 gene polymorphism on the plasma levels of lipoprotein-associated phospholipase A2 activity and mass.
abstract: Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with the development of atherosclerosis. We aimed to assess the genetic determinants of Lp-PLA2activity and mass by genotyping multiple polymorphisms in PLA2G7, the gene encoding Lp-PLA2, among 1258 participants from the Chinese Multi-provincial Cohort Study-Beijing Project. The Sequenom MassARRAY system, Taqman assay and direct sequencing were adopted. For the first time, the rs13218408 polymorphism was found to be significantly associated with reduced Lp-PLA2levels. We also confirmed the significant association of previously validated polymorphisms (rs1421378, rs1805018, rs16874954 and rs2216465), even after adjusting for traditional cardiovascular risk factors and for Bonferroni correction. Percentages of variance attributable to rs13218408 were 7.2% for activity and 13.3% for mass, and were secondary to those of rs16874954 (8.1% for activity and 16.9% for mass). A significant joint effect of rs13218408 and rs16874954 was observed on Lp-PLA2activity (P = 0.058) and mass (P = 0.003), with their minor alleles together linking to the largest reduction in Lp-PLA2levels (37.8% reduction in activity and 41.6% reduction in mass). Taken together, our findings show a significant association of a PLA2G7 polymorphism with Lp-PLA2levels, which was previously unreported in any population. The functionality of this genetic variation deserves further investigations.
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Zhangrong
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Sun
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Wuxiang
authors.initials: W
authors.lastname: Xie
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000235:genetics* / Q000276:immunology; D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human