Two variants of LPA gene associated with increased risk of coronary heart disease

Celera Corporation (NASDAQ:CRA) and its collaborators at the University of California at San Francisco today announced the publication of a paper confirming the association of an increased risk of coronary heart disease (CHD) and two variants of the LPA gene. The two LPA single nucleotide polymorphisms (SNPs) are Ile4399Met, a polymorphism in the protease-like domain of LPA, and rs10455872, a SNP located in a non-coding region of the LPA gene. The paper is available on the journal's website at http://atherosclerosis-journal.com/inpress.

“Moreover, we believe this publication will motivate functional biology follow-up studies to gain insight into the mechanistic involvement of the LPA gene in disease. These studies also emphasize the field's growing appreciation of the role of less common alleles in risk for disease.”

An independent study recently described two combinations of four variants in the LPA region that were associated with 1.8- and 1.2-fold increased risk for CHD in 6 European studies. The current study published by Celera and UCSF demonstrates that these variant combinations indirectly measure the association between CHD and the Ile4399Met and non-coding rs10455872 SNPs.

Recent studies have suggested that the Ile4399Met variant of the LPA gene is an independent predictor of risk for CHD in men and women and event reduction from low dose aspirin therapy in women. LPA encodes apolipoprotein(a), a protein component of Lp(a) plasma lipoprotein particles, and the gene variant results in an amino acid substitution (methionine for isoleucine) in the protease-like domain of apolipoprotein(a). Approximately 3.5% of Caucasians in studied populations are carriers of the Ile4399Met form of the LPA gene, and these carriers have also been found to have higher levels of plasma Lp(a). One of these studies also reported that a second LPA gene variant, rs10455872, was associated with about 1.5-fold increased risk of CHD. Approximately 15% of Caucasians in these populations were found to be carriers of the second risk variant.

"We're pleased with the publication of these data that resolve the association data of the 4-SNP combinations (haplotypes) in the LPA gene because they confirm our previously reported coronary heart disease risk findings," said Thomas White, Ph.D., Chief Scientific Officer at Celera. "Moreover, we believe this publication will motivate functional biology follow-up studies to gain insight into the mechanistic involvement of the LPA gene in disease. These studies also emphasize the field's growing appreciation of the role of less common alleles in risk for disease."