Plasma Lp Research Articles

Abstract P264: Healthy dietary interventions and Lipoprotein (a) plasma levels: Results from the Omni Heart Trial

Background: Increased lipoprotein (a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Plasma Lp(a) levels are mainly genetically determined by race with levels higher in blacks compared to whites. Dietary interventions have been reported to alter Lp(a) but evidence is sparse. No study has evaluated the effect of macronutrient composition on Lp(a) concentration and racial differences. Objective: To compare three healthy, DASH-style dietary interventions differing in macronutrient content on the effect on Lp(a) concentrations in blacks and whites. Design: Secondary analysis of a randomized, 3-period feeding study including 152 (88 blacks/64 whites) individuals. Participants were given DASH-type healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each intervention. Results: At baseline, median Lp(a) plasma level was 18 mg/dl overall, 9 mg/dl in whites and 28.5mg/dl in blacks. The Unsat Fat diet lowered Lp(a) by 1.2mg/dl (95% CI, -0.3,-2.2; p= 0.015) compared with the Carb diet, and by 2.7 mg/dl (95% CI, -1.7,-3.7; p<0.001) compared with the Prot diet (Table). The effects on Lp(a) of the controlled diets tended to be greater in blacks than whites, especially the reduction in Lp(a) on the Unsat compared to the Prot diet (-3.7 in blacks vs. -1.0 mg/dl in whites, P=0.008). On self-selected diet (prior to feeding) or intervention diets, blacks had higher mean Lp(a) than did whites. Conclusions: Compared to diets rich in carbohydrate or protein, a DASH-type diet high in unsaturated fat lowered Lp(a). These changes were greater in blacks compared to whites. Our results highlight a potential means to reduce racial disparities in CVD. Table: Differences in Lp(a) concentration (mg/dl) between study diets by ethnicity

Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients

There is considerable interest in pharmacogenetic and molecular biomarkers. Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients, such as lipoprotein(a) [Lp(a)], soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L) and serum myeloperoxidase (MPO). Three hundred and forty-five patients were enrolled in this randomized, double-blind, clinical trial: 120 hypertensive patients were randomized to enalapril 20 mg, 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination. We measures the following markers at baseline and after 6, 12, 18 and 24 months: blood pressure, fasting plasma glucose (FPG), lipid profile, Lp(a), sRAGE, sCD40L and MPO. There was a decrease in blood pressure in all groups compared with baseline, even if, as expected, enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies. No variations in lipid profile or FPG were recorded in any of the groups. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline. The combination enalapril/lercanidipine improved it more than the single therapies. All treatments increased sRAGE levels, and decreased sCD40L and MPO, with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies. The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure, but also the levels of some emerging biomarkers, potentially useful for cardiovascular risk stratification of hypertensive patients.

Lp(a)/apo(a) Modulate MMP-9 Activation and Neutrophil Cytokines in Vivo in Inflammation to Regulate Leukocyte Recruitment

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases, but the mechanism is unclear. The pathogenic risk of Lp(a) is associated with elevated plasma concentration, small isoforms of apolipoprotein [apo(a)], the unique apolipoprotein of Lp(a), and a mimic of plasminogen. Inflammation is associated with both the initiation and recovery of cardiovascular diseases, and plasminogen plays an important role in leukocyte recruitment. Because Lp(a)/apo(a) is expressed only in primates, transgenic mice were generated, apo(a)tg and Lp(a)tg mice, to determine whether Lp(a)/apo(a) modifies plasminogen-dependent leukocyte recruitment or whether apo(a) has an independent role in vivo. Plasminogen activation was markedly reduced in apo(a)tg and Lp(a)tg mice in both peritonitis and vascular injury inflammatory models, and was sufficient to reduce matrix metalloproteinase-9 activation and macrophage recruitment. Furthermore, neutrophil recruitment and the neutrophil cytokines, CXCL1/CXCL2, were suppressed in apo(a)tg mice in the abdominal aortic aneurysm model. Reconstitution of CXCL1 or CXCL2 restored neutrophil recruitment in apo(a)tg mice. Apo(a) in the plasminogen-deficient background and Lp(a)tg mice were resistant to inhibition of macrophage recruitment that was associated with an increased accumulation of apo(a) in the intimal layer of the vessel wall. These data indicate that, in inflammation, Lp(a)/apo(a) suppresses neutrophil recruitment by plasminogen-independent cytokine inhibition, and Lp(a)/apo(a) inhibits plasminogen activation and regulates matrix metalloproteinase-9 activation and macrophage recruitment.

Hyperhomocysteinemia and hyperlipoproteinemia (a) in obese south indian men: an indication for increased cardiovascular risk

Obesity is a pathological condition which increases the risk for cardiovascular disease. The present study was designed to evaluate homocysteine, lipoprotein (a) [Lp(a)], apolipoprotein-B (apo-B), apolipoprotein-A-I (apo-A-I) and lipid indices and their association if any in obese South Indian men. Thirty obese men and thirty age-matched males with normal body weight (controls) were recruited in the study. Plasma homocysteine, Lp(a), lipid profile, apo-A-I and apo-B were estimated in all the subjects. Lipid indices such as lipid pentad index (LPI), lipid tetrad index (LTI), atherogenic index of plasma (AIP), non-high density lipoprotein (non-HDL)/high density lipoprotein (HDL) ratio and apo-B/apo-A-I ratio were calculated in all study subjects. Homocysteine, Lp(a), apo-B, apo-B/apo-A-I ratio and lipid indices were significantly increased in obese men, compared to controls. Both homocysteine and Lp(a) were positively correlated with BMI, waist, hip circumference and apo-B and negatively correlated with apo-A-I. Also we found highly significant positive correlation between homocysteine and Lp(a) levels. The data from the present study concludes that non-conventional risk factors like homocysteine, Lp (a), apo-B/apo-A-I ratio, LTI, LPI, non-HDL/HDL ratio and AIP were significantly elevated in obese Indian men, suggesting they are more prone to develop cardiovascular disease, than the age-matched men with normal body weight.

La lipoproteína(a) se asocia a la presencia de arteriosclerosis en pacientes con hipercolesterolemia primaria

IntroductionSeveral studies have suggested that Lp(a) could be a risk factor mainly in hypercholesterolemic patients. MethodsA total of 909 individuals were selected for this study. 307 were diagnosed of familiar hypercholesterolemia with a pathogenic mutation in LDLR or APOB genes (FH+), 291 of familiar combined hyperlipidemia (FCH) and 311 of familial hypercholesterolemia without a pathogenic mutation in LDLR nor APOB genes (FH-). Main risk factor were studied, included statin treatment. Plasma lipids, Lp(a), HbA1c and C-reactive protein. Intima-media thickness (IMT) of common and bulb carotid in both sides were measured in all subjects. ResultsLp(a) values (median, interquartile range) were 21.9mg/dL (9.24-50.5) in FH+, 22.4mg/dL (6.56-51.6) in FCH and 32.7 (14.6-71.5) in FH- (P<.001). Regression analysis including age, gender, HDL cholesterol, LDL cholesterol corrected for Lp(a), Lp(a), C-reactive protein, packs of cigarettes/day per year, systolic blood pressure and glucose as independent variables, demonstrate that Lp(a) was associated with carotid IMT in FH- subjects. Cardiovascular disease was more frequent in subjects with Lp(a) >50mg/dL (17.9%) than in subjects with Lp(a) <15mg/dL (9.6%), and between 15-50mg/dL (10.1%), and it was concentrated mostly in FH-group (6.7, 11.3, and 23.4% for the groups of Lp(a) <15mg/dL 15-50mg/dL, and >50mg/dL, respectively). ConclusionsOur results indicate that Lp(a) is associated with atherosclerosis burden especially in subjects with FH- and concentrations of Lp(a)>50mg/dL.

Genetic determination of lipoprotein(a) and its association with cardiovascular disease: convenient does not always mean better

Genetic determination of lipoprotein(a) and its association with cardiovascular disease: convenient does not always mean better

Lipoprotein (a), LPA Ile4399Met, and Fibrin Clot Properties

Elevated lipoprotein(a) (Lp(a)) levels were reported to be associated with dense fibrin clots. The apo(a) component of Lp(a) is encoded by LPA, and the Met allele of the LPA Ile4399Met polymorphism is associated with elevated Lp(a) levels and cardiovascular disease risk. We investigated whether Ile4399Met was associated with fibrin clot properties. We determined plasma Lp(a) levels, fibrin clot permeability and lysis time for 64 LPA 4399Met carriers and 128 noncarriers matched for age, sex, ethnicity, and enrollment site. Elevated Lp(a) levels were associated with reduced clot permeability and prolonged lysis time (P<0.0001). Carriers of 4399Met had higher Lp(a) levels compared with noncarriers (P=0.0003). However, this association differed by ethnicity (P=0.003 for interaction between genotype and ethnicity): compared with noncarriers, 4399Met carriers had 2.89 fold higher Lp(a) levels among Caucasians while no difference was observed among non-Caucasians (primarily East Asians and Hispanics). Among all subjects, no association was observed between Ile4399Met and clot properties, but this relationship also differed by ethnicity: among non-Caucasians, 4399Met carriers had increased clot permeability and shorter lysis time; whereas among Caucasians, the trend was for decreased permeability and longer lysis time (P<0.01 for interactions between genotype and ethnicity). We confirmed that elevated Lp(a) levels are associated with dense fibrin clots, and found that the association of LPA 4399Met carriers and clot permeability as well as lysis time differ by ethnicity.

Effects of Fasting on Plasma Lipoprotein(a) in Cynomolgus Monkeys: Preliminary Experiments Results

Plasma lipoprotein(a) (Lp(a)) is known to be a strong independent risk factor for ischemic heart disease. However, it is not easily modulated by drugs that are presently available. Lp(a) is not present in many experimental animals except for Old World monkeys. In this study, we examined whether cynomolgus monkeys are useful model for research of human plasma Lp(a), and observed that plasma Lp(a) in cynomolgus monkeys varied as much as humans. As a result of 4 day-fasting in cynomolgus monkeys, the plasma Lp(a) level decreased in a monkey with originally high Lp(a) level. The Lp(a) level continued to decrease even 3 days after banana feeding, but returned to the original level 3 days after monkey chow feeding. On the other hand, in a monkey with low Lp(a) level, fasting had no effect on the Lp(a) level. However, in the third monkey having originally high Lp(a) level, the Lp(a) was not affected by decreasing the amount of monkey chow feeding by 50%. In summary, we found that cynomolgus monkeys may be an useful model for studying the effects of food on plasma Lp(a) in place of humans, and that high Lp(a) level may be controllable by strict diet regulation.

Screening for and Management of Elevated Lp(a)

While lipoprotein(a) (Lp(a)) has long been an intriguing subject for basic researchers and clinicians alike, it is only recently that this unique cardiovascular risk factor has begun to be broadly utilized as part of risk prediction. This has dovetailed with the recognition, from genetic studies, that Lp(a) is indeed causal for atherothrombotic disease rather than being merely a marker. Yet, significant questions remain the subject of ongoing study including: what patients groups benefit the most from determination of plasma Lp(a) concentrations; how can elevated plasma Lp(a) concentrations be most effectively managed; does reduction in plasma Lp(a) concentrations reduce risk for atherothrombotic events; and what is the molecular mechanism or mechanisms underlying the risk attributed to elevated Lp(a)? This review summarizes recent progress in genetic studies, basic laboratory research, and epidemiology with a focus on how Lp(a) might be incorporated into clinical practice.

Scavenger receptor-BI is a receptor for lipoprotein(a)

Scavenger receptor class B type I (SR-BI) is a multi-ligand receptor that binds a variety of lipoproteins, including high density lipoprotein (HDL) and low density lipoprotein (LDL), but lipoprotein(a) [Lp(a)] has not been investigated as a possible ligand. Stable cell lines (HEK293 and HeLa) expressing human SR-BI were incubated with protein- or lipid-labeled Lp(a) to investigate SR-BI-dependent Lp(a) cell association. SR-BI expression enhanced the association of both (125)I- and Alexa Fluor-labeled protein from Lp(a). By confocal microscopy, SR-BI was also found to promote the internalization of fluorescent lipids (BODIPY-cholesteryl ester (CE)- and DiI-labeled) from Lp(a), and by immunocytochemistry the cellular internalization of apolipoprotein(a) and apolipoprotein B. When dual-labeled ((3)H-cholesteryl ether,(125)I-protein) Lp(a) was added to cells expressing SR-BI, there was a greater relative increase in lipid uptake over protein, indicating that SR-BI mediates selective lipid uptake from Lp(a). Compared with C57BL/6 control mice, transgenic mice overexpressing human SR-BI in liver were found to have increased plasma clearance of (3)H-CE-Lp(a), whereas mouse scavenger receptor class B type I knockout (Sr-b1-KO) mice had decreased plasma clearance (fractional catabolic rate: 0.63 ± 0.08/day, 1.64 ± 0.62/day, and 4.64 ± 0.40/day for Sr-b1-KO, C57BL/6, and human scavenger receptor class B type I transgenic mice, respectively). We conclude that Lp(a) is a novel ligand for SR-BI and that SR-BI mediates selective uptake of Lp(a)-associated lipids.

The extended abnormalities in lipoprotein metabolism in familial hypercholesterolemia: Developing a new framework for future therapies

Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by marked elevation of plasma low-density lipoprotein (LDL) cholesterol concentrations and premature coronary artery disease (CHD). In addition to impaired LDL receptor-mediated clearance of LDL particles, in vitro and in vivo studies suggest that hepatic oversecretion of apolipoprotein (apo) B may contribute to the hypercholesterolemia in FH. This may be due to an effect of the expanded hepatic pool of cholesterol (a consequence of increased receptor-independent uptake of LDL) and/or a direct effect of the LDL receptor on apoB secretion. Hepatic oversecretion of apoB may depend on the type and severity of the genetic mutation causing FH. FH can also increase plasma Lp(a) concentration by an undefined mechanism that may not directly involve the LDL receptor pathway. Decreased catabolism of triglyceride-rich lipoproteins could also be due to deficient LDL receptor function, accounting for postprandial dyslipidemia in FH. The metabolism of high-density lipoprotein (HDL) in FH is poorly understood, but preliminary data suggest abnormal HDL composition and functionality, as well as altered transport of apoA-I. Beyond effects related to specific genetic defects in the LDL pathway, co-existing secondary causes, particularly obesity and insulin resistance, and other genetic variants may also perturb lipoprotein metabolism in individuals with FH. Furthermore, residual risk remains high in statin-treated FH. Knowledge of an extended metabolic framework will, therefore, provide the basis for judiciously selecting new pharmacotherapies to treat FH, including apoB antisense oligonucleotides, microsomal transfer protein (MTP) inhibitors and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Serum lipoprotein (a) and atherosclerotic changes in hemodialysis patients.

Introduction: Lipoprotein (a) [Lp(a)] is considered as a risk factor for coronary atherosclerotic disorder and an increase in plasma Lp(a) concentration is usually seen in patients with kidney failure. Objectives: We aimed in this study to evaluate the impact of plasma Lp(a) level on early changes of atherosclerotic vessels in stable hemodialysis (HD) patients. Patients and Methods: In this clinical study 61 patients (50 non-diabetic (F=20 M=30) and 11 diabetic HD patients), receiving maintenance hemodialysis were included and serum Lp(a) was measured. B-mode ultrasonography of carotid intima-media thickness (cIMT) was also determined. Results: The mean ±SD of patients Lp(a) was 58.5±19 mg/dL. The mean ±SD of diabetic patients’ Lp(a) was 62±12mg/dL and for nondiabetic ones was 57.7± 20mg/dL. In this study the thickening of Intima-media complex in diabetic group was more than non-diabetics, and no significant difference was found of Lp(a) between diabetic and non diabetic HD patients. There was a significant positive association between serum Lp(a) and cIMT. Conclusion: Accelerated atherosclerosis seen in diabetic hemodialysis patients. Lp(a) might have an important role in progression of atherosclerosis to accelerate progressive atherosclerosis in these patients.

Alirocumab, a Fully Human Monoclonal Antibody to PCSK9, Reduces High Plasma Lp(a) Concentration: Pooled Analysis of 352 Patients from Phase 2

Alirocumab, a Fully Human Monoclonal Antibody to PCSK9, Reduces High Plasma Lp(a) Concentration: Pooled Analysis of 352 Patients from Phase 2

Human PlasmaAnti-α-galactoside Antibody Forms Immune Complex with Autologous Lipoprotein(a)

Anti-α-galactoside antibody (anti-Gal) from human plasma that bound to α-galactoside-bearing guar galactomannan gel and was eluted with specific sugar (affinity-purified anti-Gal ; APAG) invariably contained apo(a) and apo B subunits in a proportion close to that in plasma lipoprotein(a) [ Lp(a)]. Since LDL does not contain apo(a), result suggested Lp(a) as a component of APAG. Lp(a) in APAG was complexed with anti-Gal since plate-coated anti-apo(a) captured Lp(a) along with the antibody. Association of Lp(a) with anti-Gal in APAG was considerably lower in presence of anti-Gal-specific sugar, suggesting that Lp(a) occupied the sugar-binding site of anti-Gal. Content of Lp(a)-bound anti-Gal in APAG, though a minor fraction of total antibody, increased steadily with total Lp(a) content of plasma. Further, Lp(a) released from immune complex-rich fraction of plasma by anti-Gal- specific sugar was proportional to total plasma Lp(a). Anti-Gal titre decreased with increasing Lp(a) concentration among 114 plasma samples. Results indicate the potential of anti-Gal molecules with its binding site partially occupied by Lp(a) molecule(s) to a) use the remaining binding site(s) to recognize other macromolecules or cells and b) transport Lp(a) across Fc receptor-bearing cells.

Inhibition of Neointima Formation through DNA Vaccination for Apolipoprotein(a): A New Therapeutic Strategy for Lipoprotein(a)

Lipoprotein(a) [Lp(a)] is an unique lipoprotein consisting of the glycoprotein apolipoprotein(a) [apo(a)] in low-density lipoprotein. Although Lp(a) is a well-known independent risk factor for cardiovascular disease; however, there is no drugs to decrease plasma Lp(a) level. Thus, to inhibit the biological activity of Lp(a), we developed DNA vaccine for apo(a) by the targeting to the selected 12 hydrophilic amino acids in the kringle-4 type 2 domain of apo(a). Hepatitis B virus core protein was used as an epitope carrier to enhance the immunogenicity. Intramuscular immunization with apo(a) vaccine resulted in the significant inhibition of neointima formation in carotid artery ligation model using Lp(a) transgenic mice, associated with anti-apo(a) antibody and decrease in vascular Lp(a) deposition. Overall, this study provided the first evidence that the pro-atherosclerotic actions of Lp(a) could be prevented by DNA vaccine directed against apo(a), suggesting a novel therapeutic strategy to treat cardiovascular diseases related to high Lp(a).

Association between baseline lipoprotein (a) levels and restenosis after coronary stenting: Meta-analysis of 9 cohort studies

BackgroundPrevious studies have shown inconsistent results on the association between baseline plasma Lipoprotein (a) [Lp(a)] levels and in-stent restenosis (ISR) after coronary stenting. ObjectiveWe conducted a meta-analysis of observational studies to assess the association between baseline Lp(a) levels and the restenosis after successful coronary stenting. MethodsWe searched for studies without language restriction in PubMed, Embase, Cochrane library, Ovid library database prior to October 2012. Random-effects method was applied to estimate the pooled standard mean difference (SMD). Heterogeneity, sensitivity and subgroup analysis were used to evaluate the results. Meta-regression analysis was employed to investigate sources of heterogeneity. Results9 cohort studies including 1834 patients (600 ISR and 1234 no-ISR patients) were eligible for our analysis. Overall, we found significantly elevated baseline Lp(a) levels in ISR (in-stent restenosis) patients (SMD = 0.42, 95% CI: 0.14–0.71, P = 0.003). High heterogeneity existed between the individual studies (P < 0.001, I2 = 86.9%). The association was stronger in the Asian population than the overall association found. Further, similar observations were made in the subgroup with drug-eluting stent and the group in which Lp(a) was assayed by immunoturbidimetry. Multivariable regression analysis suggested that ethnicity was the major source of heterogeneity in the data (P = 0.036). ConclusionsOur meta-analysis suggests that significantly elevated baseline plasma Lp(a) level is associated with ISR. The Lp(a) level appears to be a good predictor of ISR, especially in the Asian population or patients who received drug-eluting stent implantation. Further research is warranted to evaluate the association by taking the ethnicity and type of stent into account.

Plasma lipoprotein (a) levels in patients with slow coronary flow

IntroductionSlow coronary flow (SCF) is a microvascular disorder characterized by delayed opacification of coronary vessels with normal coronary angiogram. It may be due to endothelial dysfunction and diffuse atherosclerosis. Lipoprotein(a) [Lp(a)] is related to cardiovascular events. Plasma Lp(a) levels have not been studied previously in SCF patients.AimWe investigated plasma Lp(a) and fibrinogen levels, and their relation to coronary flow rate in patients with SCF.Material and methodsThis cross-sectional study included 50 patients with SCF and 30 age- and sex-matched controls who had normal coronary arteries and normal flow. Coronary flow rates of patients and controls were counted with the thrombolysis in myocardial infarction (TIMI) frame count. Plasma Lp(a) and fibrinogen levels were measured in SCF patients and controls, with routine biochemical tests.ResultsThere were no significant differences between the two groups with respect to plasma Lp(a) (21 mg/dl vs. 14 mg/dl, p = 0.11) and fibrinogen (278 mg/dl vs. 291 mg/dl, p = 0.48) levels. The TIMI frame count was not correlated with plasma Lp(a) (r = 0.13, p = 0.25) or fibrinogen (r = –0.14, p = 0.28) levels.ConclusionsOur results show that there is no significant association between SCF and Lp(a) and fibrinogen levels.

Association between high molecular weight apolipoprotein isoforms and lipoprotein levels in advanced chronic kidney disease and the effect of hemodialysis

To explore the association between high molecular weight apo(a) isoforms and lipoprotein(a) [Lp(a)] in chronic kidney disease (CKD) and the effect of maintenance hemodialysis (MHD), plasma Lp(a) and apo(a) isoforms were determined in age and sex-matched CKD stage 4 and stage 5 patients (repeated after 4 weeks of MHD) and healthy controls (n = 18). Median Lp(a) increased with severity of CKD. Upon HMW apo(a) isoform stratification, Lp(a) in S2 isoform group was 37.6 mg/dl in CKD stage 4 and 64.0 mg/dl in stage 5 (P < 0.024 and P < 0.001 vs. controls), whereas in S3 + S4 group there was no significant increase. Following MHD, Lp(a) also decreased significantly only in the S2 group. Increase in Lp(a) in CKD patients with HMW apo(a) isoforms is mainly restricted to S2 isoform group, furthermore, decrease in Lp(a) levels in response to MHD is also seen in this group only.

Lipoprotein apheresis in isolated hyperlipoproteinemia(a): a validated treatment or an illusion of validity?

Lipoprotein apheresis in isolated hyperlipoproteinemia(a): a validated treatment or an illusion of validity?

Lack of association between four SNPs in the SLC22A3-LPAL2-LPA gene cluster and coronary artery disease in a Chinese Han population: a case control study

BackgroundLipoprotein (a) (Lp [a]) is known being correlated with coronary artery disease (CAD). The SLC22A3-LPAL2-LPA gene cluster, relating with modulating the level of plasma Lp (a), has recently been reported to be associated with CAD in Caucasians. The purpose of this study was to verify whether this finding can be expanded to the Chinese Han population.Methods and ResultsUsing a Chinese Han sample, which consisted of 1012 well-characterized CAD patients and 889 healthy controls, we tested the associations of four SNPs (rs2048327, rs3127599, rs7767084 and rs10755578) in the SLC22A3-LPAL2-LPA gene cluster, and their inferred haplotypes with the risk of CAD. Allelic, genotypic and haplotype association analyses all showed that the gene cluster was not associated with CAD in this Chinese Han sample.ConclusionsWe for the first time explored the association of the four SNPs in the SLC22A3-LPAL2-LPA gene cluster with CAD in a large Chinese Han sample. Nevertheless, this study did not reveal any significant evidence of this gene cluster to increase the risk of CAD in this population.