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Association of Lp-PLA(2) activity with allele-specific Lp(a) levels in a bi-ethnic population.

ABSTRACT: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and lipoprotein(a) [Lp(a)] have been implicated as cardiovascular disease risk factors, and are differentially regulated across ethnicity. We investigated the association between Lp-PLA(2) activity and allele-specific apolipoprotein(a) [apo(a)] levels in a bi-ethnic population.Lp-PLA(2) activity, Lp(a) and allele-specific apo(a) levels were determined in 224 African Americans and 336 Caucasians.Lp-PLA(2) activity level was higher among Caucasians compared to African Americans (173 + or - 41 nmol/min/ml vs. 141 + or - 39 nmol/min/ml, P<0.001), and positively associated with Lp(a), total and LDL cholesterol, triglyceride, apolipoprotein B-100, and negatively with HDL cholesterol levels in both ethnic groups. The association between Lp-PLA(2) activity and Lp(a) was stronger among African Americans compared to Caucasians (R=0.238, beta(1)=3.48, vs. R=0.111, beta(1)=1.93, respectively). The Lp-PLA(2) activity level was significantly associated with allele-specific apo(a) levels for smaller (<26 K4 repeats) apo(a) sizes in both ethnic groups (P=0.015 for African Americans, P=0.038 for Caucasians). In contrast, for larger (>26 K4 repeats) apo(a) sizes, high Lp-PLA(2) activity levels were associated with higher allele-specific apo(a) levels in African Americans (P=0.009), but not in Caucasians.The association between Lp-PLA(2) activity and allele-specific apo(a) levels differs across African American-Caucasian ethnicity.

SUBMITTER: Enkhmaa B

PROVIDER: S-EPMC2914160 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Association of Lp-PLA(2) activity with allele-specific Lp(a) levels in a bi-ethnic population.

Enkhmaa Byambaa B Anuurad Erdembileg E Zhang Wei W Pearson Thomas A TA Berglund Lars L

Atherosclerosis 20100420 2

<h4>Objectives</h4>Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and lipoprotein(a) [Lp(a)] have been implicated as cardiovascular disease risk factors, and are differentially regulated across ethnicity. We investigated the association between Lp-PLA(2) activity and allele-specific apolipoprotein(a) [apo(a)] levels in a bi-ethnic population.<h4>Methods</h4>Lp-PLA(2) activity, Lp(a) and allele-specific apo(a) levels were determined in 224 African Americans and 336 Caucasians.<h4>Results</ ...[more]

PMID: 20444451

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Project description:BackgroundTo examine the association between lipoprotein(a) (Lp(a)) levels, LPA (rs10455872 and rs3798220) and IL1F9 (rs13415097) single nucleotide polymorphisms (SNPs) with coronary artery calcification (CAC), an important predictor for coronary artery disease (CAD).MethodsWe used data from 3799 (mean age ± SD: 59.0 ± 7.7 years, 47.1% men) Heinz Nixdorf Recall study participants. We applied linear regression models to explore the relation between the log-transformed Lp(a) levels and LPA and IL1F9 SNPs with loge (CAC + 1). The association between the SNPs and log-transformed Lp(a) levels was further assessed using linear regression. The models were adjusted for age and sex (Model 1) and additionally for Lp(a) levels (Model 2).ResultsWe observed a statistically significant association between log-transformed Lp(a) levels and CAC (Model 1: beta per log-unit increase in Lp(a) levels = 0.11; 95% confidence interval [95% CI] [0.04; 0.18], p = 0.002). Furthermore, the LPA SNP rs10455872 showed a statistically significant association with CAC (Model 1: beta per allele = 0.37 [0.14; 0.61], p = 0.002). The association between rs10455872 and CAC was attenuated after adjustment for Lp(a) levels (Model 2: beta per allele = 0.26 [- 0.01; 0.53], p = 0.06). Both LPA SNPs also showed a statistically significant association with Lp(a) levels (Model 1: betars10455872 per allele: 1.56 [1.46; 1.65], p < 0.0001 and betars3798220 per allele: 1.51 [1.33; 1.69], p < 0.0001)). The Mendelian randomization analysis showed that Lp(a) is a causal risk factor for CAC (estimate per log-unit increase in Lp(a) levels (95% CI), p: 0.27 [0.11; 0.44], p = 0.001). The IL1F9 SNP did not show any statistically significant association with Lp(a) levels or with CAC.ConclusionsWe provide evidence for the association of LPA rs10455872 with higher levels of Lp(a) and CAC in our study. The results of our study suggest that rs10455872, mediated by Lp(a) levels, might play a role in promoting the development of atherosclerosis leading to cardiovascular disease events.

Dataset Information

Association of Lp-PLA(2) activity with allele-specific Lp(a) levels in a bi-ethnic population.

Publications

Association of Lp-PLA(2) activity with allele-specific Lp(a) levels in a bi-ethnic population.

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