Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Neither polyphenol-rich red wine nor fenofibrate affects the onset of type-1 diabetes mellitus in the BB rat / 한국실험동물학회지

Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was also increased in sera from pre-diabetic rats and this promoted β-cell death. Lowering apoCIII with an oligonucleotide antisense during a phase of the pre-diabetic period prolonged the time to onset of T1D. In order to find other ways to lower apoCIII we in this study tested non-alcoholic red wine with medium and high concentrations of polyphenols and the lipid-lowering drug, fenofibrate, both reported to decrease the expression of apoCIII by activating peroxisome proliferator-activated receptors. Pre-diabetic BB-rats were treated orally for one month prior to the expected onset of diabetes with the two different wines or fenofibrate. None of the treatments prevented or prolonged the time to onset of diabetes and the expression of apoCIII was unaffected in this animal model for T1D. However, it must be emphasized that this does not exclude that other species can show a response to these substances.

Plasma apoCIII Levels in Relation to Inflammatory Traits and Metabolic Syndrome in Patients not Treated with Lipid-lowering Drugs Undergoing Coronary Angiography / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Assessment of the comprehensive relationship among apolipoprotein CIII (apoCIII) levels, inflammation, and metabolic disorders is rare.</p><p><b>METHODS</b>A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCIII in the association of inflammation with metabolic syndrome (MetS).</p><p><b>RESULTS</b>Patients with MetS showed higher levels of apoCIII [95.1 (73.1-131.4) vs. 81.7 (58.6-112.4) μg/mL, P < 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7 (0.8-3.4) vs. 1.1 (0.5-2.2) mg/L; white blood cell count, (6.48 ± 1.68) vs. (6.11 ± 1.67) × 109/L]. The levels of apoCIII and inflammatory markers increased with the number of metabolic risk components (all P < 0.001). Furthermore, apoCIII levels were associated with virtually all individual MetS risk factors and inflammatory markers (all P < 0.05). Importantly, the prevalence of MetS in each metabolic disorder rose as apoCIII levels increased (all P < 0.05). Mediation analysis showed that apoCIII partially mediated the effect of inflammation on MetS independently from triglycerides.</p><p><b>CONCLUSION</b>Plasma apoCIII levels were significantly associated with the development and severity of MetS, and a role of apoCIII in the effect of inflammation on the development of MetS was identified.</p>

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Apolipoprotein CIII (apo-CIII) participates in the regulation of triglyceride-rich lipoprotein metabolism. Several polymorphic sites have been detected within and around the apo-CIII gene. Here, we examined the relationship between apo-CIII SstI polymorphism (CC, CG, GG genotypes) and plasma triglyceride (TG) levels in a group of 159 Japanese individuals living in Southern Brazil. The sample was divided into a group of Japanese descendants (N = 51) with high TG (HTG; >200 mg/dL) and a group of Japanese descendants (N = 108) with normal TG (NTG; <200 mg/dL). TG and total cholesterol levels were analyzed by an enzymatic method using the Labtest-Diagnostic kit and high- and low-density lipoproteins by a direct method using the Labtest-Diagnostic kit and DiaSys Diagnostic System International kit, respectively. A 428-bp sequence of apo-CIII gene was amplified using oligonucleotide primers 5' GGT GAC CGA TGG CTT CAG TTC CCT GA 3' and 5' CAG AAG GTG GAT AGA GCG CTG GCC T 3'. The PCR products were digested with a restriction endonuclease SstI. Rare G allele was highly prevalent in our study population (0.416) compared to Caucasians (0.00-0.11). G allele was almost two times more prevalent in the HTG group compared to the NTG group (P < 0.001). The genotype distribution was consistent with the Hardy-Weinberg equilibrium. There was a significant association between rare G allele and HTG in Japanese individuals living in Southern Brazil as indicated by one-way ANOVA, P < 0.05.

Variation of the promoter of apolipoprotein C-III with hyperlipidemic patients / 대한내과학회지

BACKGROUND: Hypertriglyceridemia and hypercholesterolemia have been associated with atherosclerosis, myocaridal infarction, and premature death. However, the causes of hyperlipidemia are not well understood. Variations in apolipoprotein C-III (apo C-III) are candidate for contributing to the occurrence of hypertriglyceridemia. A genetically variant form of human apo C-III promoter, containing five single base pair changes, has been shown that it seems to be associated with hypertriglyceridemia. Especially, the loss of insulin regulation was mapped to polymorphic sites at -482 and -455, which fall within an insulin response element. METHODS: We studied 146 subjects with hyperlipidemia and also had 94 controls. Screening for mutations at codon -482 and -455 of apo C-III promoter were carried out by PCR-RFLP analyses. RESULTS: 1) In the codon -482 site of the patient group, the genotype frequency of T/T homozygote was higher than in the control group, whereas the frequency of T/C heterozygote and C/C homozygote were lower. 2) Serum triglyceride related to genotype shows positive correlation trend with freguency of -482 T allele and -455 C allele, but has not stastistical significancy. 3) In complete mutated groups of both -482 T/T and -455 C/C in hyperlipidemia patients, serum triglyceride and fasting blood glucose are higher than in wild type groups of both -482 C/C and -455 T/T. CONCLUSION: We suggest that variations of the promoter of apolipoprotein C-III may be a genetic marker in patients with hyperlipidemia.