LPA variants, apo(a) isoforms and events differ by ethnicity: the Dallas Heart Study (Lee et al., Circulation 2017)

Original title: LPA Gene, Ethnicity, and Cardiovascular Events

Circulation · 17 January 2017 · 6

Lee SR, Prasad A, Choi YS, Xing C, Clopton P, Witztum JL, Tsimikas S

In 1,792 Black, 1,030 White and 597 Hispanic participants followed 9.5 years, the prevalence of the LPA SNPs and their relation to isoform size varied widely by group (rs3798220 in 42 percent of Hispanics, rs10455872 in 14 percent of Whites, rs9457951 in 33 percent of Blacks); the top quartile of Lp(a) carried a hazard ratio for MACE of 2.35 overall, with ethnicity-specific patterns for isoform size and OxPL-apoB. Genotype is not a substitute for measurement outside European populations.

Original abstract

Background: The relationship of LPA single nucleotide polymorphisms (SNPs), apolipoprotein(a) isoforms, and lipoprotein(a) [Lp(a)] levels with major adverse cardiovascular events (MACE) in different ethnic groups is not well known.

Methods: LPA SNPs, apolipoprotein(a) isoforms, Lp(a), and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels were measured in 1792 black, 1030 white, and 597 Hispanic subjects enrolled in the Dallas Heart Study. Their interdependent relationships and prospective association with MACE after median 9.5-year follow-up were determined.

Results: LPA SNP rs3798220 was most prevalent in Hispanics (42.38%), rs10455872 in whites (14.27%), and rs9457951 in blacks (32.92%). The correlation of each of these SNPs with the major apolipoprotein(a) isoform size was highly variable and in different directions among ethnic groups. In the entire cohort, Cox regression analysis with multivariable adjustment revealed that quartiles 4 of Lp(a) and OxPL-apoB were associated with hazard ratios (95% confidence interval) for time to MACE of 2.35 (1.50-3.69, P<0.001) and 1.89 (1.26-2.84, P=0.003), respectively, versus quartile 1. Addition of the major apolipoprotein(a) isoform and the 3 LPA SNPs to these models attenuated the risk, but significance was maintained for both Lp(a) and OxPL-apoB. Evaluating time to MACE in specific ethnic groups, Lp(a) was a positive predictor and the size of the major apolipoprotein(a) isoform was an inverse predictor in blacks, the size of the major apolipoprotein(a) isoform was an inverse predictor in whites, and OxPL-apoB was a positive predictor in Hispanics.

Conclusions: The prevalence and association of LPA SNPs with size of apolipoprotein(a) isoforms, Lp(a), and OxPL-apoB levels are highly variable and ethnicity-specific. The relationship to MACE is best explained by elevated plasma Lp(a) or OxPL-apoB levels, despite significant ethnic differences in LPA genetic markers.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.