Apolipoprotein H Variant Modifies Plasma Triglyceride Phenotype in Familial Hypercholesterolemia: A Molecular Study in an Eight-generation Hyperlipidemic Family.

Takada, Daisuke; Ezura, Yoichi; Ono, Shuji; Iino, Yuichi; Katayama, Yasuo; Xin, Yuanpei; Wu, Lily; Larringa-Shum, Stacey; Stephenson, Susan; Hunt, Steven C.; Hopkins, Paul N.; Emi, Mitsuru

doi:10.5551/jat.10.79

Cited by 21 publications

(8 citation statements)

References 25 publications

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“…Plasma apolipoprotein H (apo H) concentrations have also been found to change with hyperlipidemia (Takada et al., 2003). Plasma apo H concentrations changed differently over time in the 3 groups (time × group interaction, p = 0.0001, Fig.…”

Section: Resultsmentioning

confidence: 99%

Individual Differences in Hyperlipidemia and Vitamin E Status in Response to Chronic Alcohol Self-Administration in Cynomolgus Monkeys

Lebold

Grant

Freeman

et al. 2010

Alcoholism: Clinical and Experimental Research

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Background Chronic ethanol self-administration induces oxidative stress and exacerbates lipid peroxidation. α-Tocopherol is a potent lipid antioxidant and vitamin that is dependent upon lipoprotein transport for tissue delivery. Methods To evaluate the extent to which vitamin E status is deranged by excessive alcohol consumption, monkeys voluntarily drinking ethanol (1.36 to 3.98 g/kg/day for 19 months, n=11) were compared with non-drinkers (n=5, control) Results Three alcohol drinking animals developed hyperlipidemia with plasma triglyceride levels (1.8 ± 0.9 mmol/L) double those of normolipidemic (NL) drinkers (0.6 ± 0.2) and controls (0.6 ± 0.3, p<0.05); elevated plasma cholesterol (3.6 ± 0.5 mmol/L) compared with NL drinkers (2.3 ± 0.2, p<0.05) and controls (2.9 ± 0.3); and lower plasma α-tocopherol per triglycerides (14 ± 6 mmol/mol) than controls (27 ± 8) and NL drinkers (23 ± 6 p<0.05). Hyperlipidemic monkey liver α-tocopherol (47 ± 15 nmol/g) was lower than NL drinkers (65 ± 13) and controls (70 ± 15, p=0.080), as was adipose α-tocopherol (84 ± 37nmol/g) compared with controls (224 ± 118) and NL drinkers (285 ± 234, p<0.05). Plasma apolipoprotein (apo) CIII increased compared to baseline at both 12 and 19 months in the normolipidemic (P=0.0016 and P=0.0028, respectively) and in the hyperlipidemic drinkers (P<0.05 and P<0.05, respectively). Plasma apo H concentrations at 19 months were elevated hyperlipidemics (P<0.05) relative to concentrations in control animals. C-reactive protein (CRP), a marker of inflammation, was increased compared to baseline at both the 12- and 19-month time points in the normolipidemic (P=0.005 and P=0.0153, respectively) and hyperlipidemic drinkers (P=0.016 and P=0.0201, respectively). Conclusion A subset of alcohol drinking monkeys showed a predisposition to alcohol-induced hyperlipidemia. The defect in lipid metabolism resulted in lower plasma α-tocopherol per triglycerides and depleted adipose tissue α-tocopherol, and thus, decreased vitamin E status.

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Section: Resultsmentioning

confidence: 99%

Individual Differences in Hyperlipidemia and Vitamin E Status in Response to Chronic Alcohol Self-Administration in Cynomolgus Monkeys

Lebold

Grant

Freeman

et al. 2010

Alcoholism: Clinical and Experimental Research

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“…Genetic variation at splice sites, leading to population splice variation, has been observed as mutations in family studies 30,31 and as population polymorphisms. 32 However, to our knowledge, this represents the first instance in which a splice variant accounts for the molecular basis of a classical protein polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus

et al. 2008

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Electrophoretic analysis of protein variation at the coagulation F13B locus has previously revealed three alleles, with alleles 1, 2, and 3 each being at high frequency in European, African, and Asian populations, respectively. To determine if this unusual pattern of interpopulation differentiation reflects local natural selection or neutral genetic drift, we re-sequenced 4.6 kb of the gene, encompassing all exons, splice junctions, and 1.4 kb of the promoter, in African, European, and Asian samples. These analyses revealed three major lineages, which correspond to the common protein alleles and differ from each other at a nonsynonymous substitution in exon 3 and a novel splice acceptor in intron K. There is previous evidence that these lineages are not functionally equivalent; we therefore carried out case -control analyses and confirmed that variability at F13B modulates susceptibility and/or survivorship in coronary artery disease (Po0.05) and type II diabetes within the coronary artery disease cohort (Po0.01). Tajima's D and Fu and Li's tests did not indicate significant departures from neutral expectations. However, publicly available data from SeattleSNPs and HapMap do indicate highly unusual levels of population differentiation (P ¼ 0.003) and an excess of allele-specific, extended haplotype homozygosity within the African population (P ¼ 0.0125). Possible causes of this putative signal of selection include hematophagous organisms, infection by pathogens that cause disseminated intravascular coagulation, and metabolic or dietary factors.

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“…CHKA plays an important role in phospholipid biosynthesis via the CDPcholine pathway [24]. APOH, also called β2 glycoprotein I, may be involved in triglyceride-rich lipoprotein clearance by activation of lipoprotein lipase [25]. In this study, CHKA was significantly upregulated in the liver of LRFI ducks, and APOH was significantly upregulated in the duodenal epithelium of LRFI ducks.…”

Section: Discussionmentioning

confidence: 51%

Expression of genes related to lipid transport in meat-type ducks divergent for low or high residual feed intake

Jin

Zang

et al. 2020

Asian-Australas J Anim Sci

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Objective: This study examined the effects of divergence in residual feed intake (RFI) on expression profiles of key genes related to lipid transport in the liver and duodenal epithelium and their associations with feed efficiency traits in meat-type ducks. Methods: A total of 1,000 male ducks with similar body weight (1,042.1±87.2 g) were used in this study, and their individual RFI was calculated from 21 to 42 d of age. Finally, the 10 highest RFI (HRFI) and 10 lowest RFI (LRFI) ducks were chosen for examining the expression of key genes related to lipid transport in the liver and duodenal epithelium using quantitative polymerase chain reaction. Results: In the liver, expression levels of albumin (ALB), CD36 molecule (CD36), fatty acid hydroxylase domain containing 2 (FAXDC2), and choline kinase alpha (CHKA) were significantly higher in LRFI ducks than in HRFI ducks (p<0.01); negative correlations (p<0.05) between expression levels of ALB, CD36, FAXDC2, and CHKA and RFI were detected in the liver. Additionally, ALB expression was strongly positively correlated (p<0.05) with CD36, FAXDC2, CHKA, and apolipoprotein H (APOH) expression in the liver. In duodenal epithelium, we found that mRNA levels of ALB, CD36, FAXDC2, and APOH were significantly higher in LRFI ducks than in HRFI ducks (p<0.01); RFI was strongly negatively correlated (p<0.05) with ALB, FAXDC2, and APOH expression, while ALB expression was strongly positively correlated with APOH expression (p<0.01) in duodenal epithelium. Furthermore, expression levels of both ALB and FAXDC2 genes were significantly associated with feed conversion ratio and RFI in both liver and duodenal epithelium (p<0.05). Conclusion: Our findings therefore suggest that ALB and FAXDC2 genes might be used as potential gene markers designed to improve feed efficiency in future meat-type duck breeding programs.

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Apolipoprotein H Variant Modifies Plasma Triglyceride Phenotype in Familial Hypercholesterolemia: A Molecular Study in an Eight-generation Hyperlipidemic Family.

Cited by 21 publications

References 25 publications

Individual Differences in Hyperlipidemia and Vitamin E Status in Response to Chronic Alcohol Self-Administration in Cynomolgus Monkeys

Individual Differences in Hyperlipidemia and Vitamin E Status in Response to Chronic Alcohol Self-Administration in Cynomolgus Monkeys

Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus

Expression of genes related to lipid transport in meat-type ducks divergent for low or high residual feed intake

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