ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study

Anuurad, Erdembileg; Lu, Guijing; Rubin, Jill; Pearson, Thomas A.; Berglund, Lars

doi:10.1194/jlr.m600431-jlr200

Cited by 19 publications

(18 citation statements)

References 46 publications

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“…However, this was not the case in our population, where we found no significant association between ε4-carrier status and baseline TC and LDL. The associations between the apoE polymorphism and plasma concentrations of HDL, apoA, Lp(a) and triglycerides have been more inconsistent in the literature, with results that range from no association[18,19] to associations that vary by sex [20]. We found no association between those lipid traits and ε4-carrier status in our population.…”

Section: Discussioncontrasting

confidence: 68%

Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy

et al. 2011

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BackgroundThe risk of coronary heart disease (CHD) is related to environmental factors and genetic variants. Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol, with some authors suggesting an association between the ε4 allele and CHD. We investigated the relationship between apoE genotype and age at referral to a specialized lipid clinic by the primary care physician and whether the benefits of treatment with statin differed between genotypes.MethodsWe assessed individual apoE genotypes and lipid blood profile in a total of 463 patients followed at a specialized lipid clinic due to dyslipidemia, with a 3-year median follow-up time. The primary care physician at the time of the referral had no access to the apoE genotyping results. Carriers of apoE ε4/ε2 genotype were excluded.ResultsThe frequencies of ε2, ε3 and ε4 alleles were 7.8, 78.9 and 13.3%, respectively. There were no significant differences between genders. Although with similar lipid profiles and antidyslipidemic drug usage at baseline, ε4-carriers were referred to the clinic at a younger age (44.2 ± 14.7 years) compared with non-ε4 carriers (50.6 ± 13.8 years) (p < 0.001), with a substantially younger age of referral for homozygous E4/4 and for all genotypes with at least one copy of the ε4 allele (p < 0.001 for trend). Although both ε4 and non-ε4 carriers achieved significant reductions in total cholesterol during follow-up (p < 0.001 vs. baseline), the mean relative decrease in total cholesterol levels was higher in non-ε4 carriers (-19.9 ± 2.3%) compared with ε4 carriers (-11.8 ± 2.3%), p = 0.003.ConclusionOur findings support the concept that there is a reduced response to anti-dyslipidemic treatment in ε4 carriers; this can be a contributing factor for the earlier referral of these patients to our specialized lipid clinic and reinforces the usefulness of apoE genotyping in predicting patients response to lipid lowering therapies.

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Section: Discussioncontrasting

confidence: 68%

Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy

et al. 2011

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“…Some allele frequencies were markedly different from those reported in other populations. The APOE E4 allele frequency for the Greenlanders was similar to Canadian Inuit (0.230) (24) but higher than in Caucasians (0.138) (25). The APOE E2 allele in Greenlanders was somewhat more frequent compared with Canadian Inuit (0.010) (24) but less frequent when compared with Caucasians (0.082) (25).…”

Section: Baseline Demographic Featuresmentioning

confidence: 86%

“…The APOE E4 allele frequency for the Greenlanders was similar to Canadian Inuit (0.230) (24) but higher than in Caucasians (0.138) (25). The APOE E2 allele in Greenlanders was somewhat more frequent compared with Canadian Inuit (0.010) (24) but less frequent when compared with Caucasians (0.082) (25). The APOC3 -455C allele was less frequent in Greenlanders compared with Canadian Inuit (0.478) (Pollex and Hegele, unpublished data) but more frequent when compared with Caucasians (0.35) (26).…”

Section: Baseline Demographic Featuresmentioning

confidence: 99%

Common variants APOC3, APOA5, APOE and PON1 are associated with variation in plasma lipoprotein traits in Greenlanders

Lahiry

Ban

Pollex

et al. 2007

International Journal of Circumpolar Health

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Objectives. We undertook studies of the association between common genomic variations in APOC3, APOA5, APOE and PON1 genes and variation in biochemical phenotypes in a sample of Greenlanders. Study design. Genetic association study of quantitative lipoprotein traits. Methods. In a sample of 1,310 adult Greenlanders, fasting plasma lipid, lipoprotein and apolipoprotein (apo) concentrations were assessed for association with known functional genomic variants of APOC3, APOA5, APOE and PON1. For significantly associated polymorphisms, between-genotype differences were examined in closer detail. Results. We found that (1) the APOE restriction isotype was associated with variation in plasma total and LDL cholesterol and apo B (all p<.0001); (2) the APOC3 promoter genotype was associated with variation in plasma triglycerides, HDL cholesterol and apo A-I (all p<.002); (3) the APOA5 codon 19 genotype was associated with variation in plasma triglycerides (p=.027); and (4) the PON1 codon 192 genotype was associated with variation in total and LDL cholesterol and apo B (all p<.05). Conclusions. Taken together, our results suggest that common genetic variations in APOC3, APOA5, APOE and PON1 are associated with significant variation in intermediate traits in plasma lipoprotein metabolism in Greenlanders; the associations are similar to those observed for these variants in other populations. (Int J Circumpolar Health 2007; 66(5): 390-400)

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“…The clinical characteristics of the study population and the study design, including inclusion and exclusion criteria, have been described previously, and notably, exclusion criteria included use of lipid-lowering drugs (16,21). Briefly, a total of 648 patients, 401 men and 247 women, ethnically selfidentified as Caucasian (n 5 344), African American (n 5 232), or Other (n 5 72) were enrolled.…”

Section: Subjectsmentioning

confidence: 99%

“…ApoE genotypes were determined as described previously (16,21,28). Genotypic status for the HpaI apoC-I promoter polymorphism was determined as described by a two-step nested PCR followed by restriction digestion with HpaI and electrophoresis on 1.5% agarose (ultraPure Agarose, Life Technologies, Gaithersburg, MD) (18).…”

Section: Determination Of Apoe and Apoc-i Genotypesmentioning

confidence: 99%

ApoE and ApoC-I polymorphisms: association of genotype with cardiovascular disease phenotype in African Americans

Anuurad

Yamasaki

Shachter

et al. 2009

Journal of Lipid Research

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ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study

Cited by 19 publications

References 46 publications

Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy

Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy

Common variants APOC3, APOA5, APOE and PON1 are associated with variation in plasma lipoprotein traits in Greenlanders

ApoE and ApoC-I polymorphisms: association of genotype with cardiovascular disease phenotype in African Americans

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