Article

APOC3 mutation, serum triglyceride concentrations, and coronary heart disease.

Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA.
Clinical Chemistry (Impact Factor: 7.15). 06/2009; 55(7):1274-6. DOI: 10.1373/clinchem.2009.124669
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    ABSTRACT: APOA1/C3/A4/A5 gene cluster is closely involved in lipid metabolism, and its polymorphisms have been associated with coronary heart disease and lipid plasma levels. Here, we aimed to investigate associations of APOC3 (3238C>G, -482C>T, 1100C>T) and APOA4 (Gln360His, Thr347Ser) polymorphisms in 382 individuals from a cohort of a Longitudinal Brazilian Elderly Study with major age-related morbidities and with lipid and protein serum levels. The whole sample was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Descriptive statistics, logistic regression analysis, Student t test, deviation from Hardy-Weinberg, Bonferroni correction for multiple testing, and haplotype analyses were performed. Although APOC3 1100T allele carriers presented lower triglyceride and very low density lipoprotein levels than non-T carriers, these associations disappeared after Bonferroni correction (P > 0.05). Moreover, APOA4 360His allele was associated with depression (P = 0.03), increased triglyceride (P = 0.035) and very low density lipoprotein (P = 0.035) levels, and reduced HDL levels (P = 0.0005). Haplotype analyses found an association between His/C/C haplotype (Gln360His/-482C>T/1100C>T) with depression, but this result was due to Gln360His polymorphism. Our data suggest that 360His allele might be a risk factor for depression and unfavorable lipid profile and depression for elderly people in the Brazilian population.
    Journal of Investigative Medicine 06/2011; 59(6):966-70. · 1.75 Impact Factor
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    ABSTRACT: Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG.
    Lipids in Health and Disease 01/2010; 9:86. · 2.31 Impact Factor
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    ABSTRACT: Introduction: APOA1/C3/A4/A5 gene cluster is closely involved in lipid metabolism, and its polymorphisms have been associated with coronary heart disease and lipid plasma levels. Here, we aimed to investigate associations of APOC3 (3238C>G, −482C>T, 1100C>T) and APOA4 (Gln360His, Thr347Ser) polymorphisms in 382 individuals from a cohort of a Longitudinal Brazilian Elderly Study with major age-related morbidities and with lipid and protein serum levels. Materials and Methods: The whole sample was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Descriptive statistics, logistic regression analysis, Student t test, deviation from Hardy-Weinberg, Bonferroni correction for multiple testing, and haplotype analyses were performed. Results: Although APOC3 1100T allele carriers presented lower triglyceride and very low density lipoprotein levels than non-T carriers, these associations disappeared after Bonferroni correction (P > 0.05). Moreover, APOA4 360His allele was associated with depression (P = 0.03), increased triglyceride (P = 0.035) and very low density lipoprotein (P = 0.035) levels, and reduced HDL levels (P = 0.0005). Haplotype analyses found an association between His/C/C haplotype (Gln360His/−482C>T/1100C>T) with depression, but this result was due to Gln360His polymorphism. Conclusions: Our data suggest that 360His allele might be a risk factor for depression and unfavorable lipid profile and depression for elderly people in the Brazilian population.
    Journal of Investigative Medicine 07/2011; 59(6):966-970. · 1.75 Impact Factor

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