ApoCIII Gene Variants Modulate Postprandial Response to Both Glucose and Fat Tolerance Tests

Abstract

on behalf of the EARS Group Background-We investigated the relationship between variation in the apolipoprotein (apo) AI-CIII-AIV gene cluster and response to an oral glucose test (OGTT) and oral fat load test (OFTT) in the EARSII group of young, healthy male offspring whose fathers had had a myocardial infarction before the age of 55 years (cases, nϭ407) compared with age-matched controls (nϭ415). The apoCIII variations examined were C3238G (SstI) in the 3Ј-UTR, C1100T in exon 3, C-482T in the insulin response element (IRE), and T-2854G in the apoCIII-AIV intergenic region. Methods and Results-The postprandial response was regulated by variation at the T-2854G and C3238G sites. After the OFTT, carriers of the rare alleles had delayed clearance of triglyceride (Tg)

Variable effects of the APOC3 -482C > T variant on insulin, glucose and triglyceride concentrations in different ethnic groups

“…These results confirm our previous findings of an association with the T-482 allele and hyperinsulinaemia in white subjects, though in the original study the association was with insulin after an OGTT [4] and not with fasting concentrations as in this study. Although the previous study was larger (n = 800), it was carried out in healthy young men as opposed to the middle-aged men and women (n = 462) who participated in this study.…”

“…Fasting insulin, glucose and triglyceride measurements were obtained in all subjects and 2-h insulin and glucose in 78 % of the white subjects, 71 % of South Asians and 71 % of black subjects. Genomic DNA was isolated from whole blood [8] and assay conditions were as described previously [4]. Data were tested for deviation from Hardy-Weinberg equilibrium using a chisquared test (on 1 degree of freedom).…”

“…is associated with higher insulin and glucose concentrations after an OGTT in young, healthy white European men participating in the second European Atherosclerosis Research Study [4]. The presence of the ±482T allele has been shown in vitro to abolish the normal down-regulation of ApoCIII by insulin [5].…”

Population prevalence of APOE, APOC3 and PPAR-α mutations associated to hypertriglyceridemia in French Canadians

“…Among genetic variations located in the APOC3 locus, several SNPs have been associated with lipoprotein metabolism. The first APOC3 marker, the C-482T polymorphism, was reported to be associated with plasma TG levels in adult aboriginal Canadian (Hegele et al 1997), remnant-like particles TG (Waterworth et al 2000), apoB-containing particles or TG-related a Population from the Rockefeller University Hospital or members of the university community (Dammerman et al 1993) b ARIC population from four different US cities (Surguchov et al 1996) c EARS control population from 11 European countries divided into four regions: Baltic, United kingdom; Middle Europe and South Europe (Waterworth et al 1999) d…”

“…Lille population composed of 495 men and 176 women living in the urban community of Lille (Dallongeville et al 2001) e Czech Slav population (Waterworth et al 2000) f Italian population recruited from five schools in the tenth district of Rome (Shoulders et al 1996) g Population living at 2,000 km Northwest of Toronto, Ontario (Hegele et al 1997) (Hegele et al 1995) b Population from the Rockefeler University Hospital or members of the university community (Dammerman et al 1993) c Control population from the Framingham cohort (Ordovas et al 1991) d ARIC population from four different US cities (Surguchov et al 1996) e EARS control population came from 11 European countries divided into four regions: Baltic, United kingdom; middle Europe and southern Europe (Waterworth et al 1999) f Europeans came from the European Union Biomedical Project comprising subjects with no personal or familial history of coronary heart disease and from Germany, Spain and Italy (Zhang et al 1998) g Broader population survey on cardiovascular risk factors h Population from Scotland was control men without coronary heart disease history (Rees et al 1983) i Utrecht are spouses of Dutch Caucasians FCHL recruited from the lipid clinic of the University Medical Centre Utrecht (Groenendijk et al 2001) j Italian population recruited from five schools in the tenth district of Rome (Shoulders et al 1996) k Population from London was healthy controls (Price et al 1989) markers (Dallongeville et al 2000). Furthermore, the G3238 allele was found to be associated with HTG in different populations, such as Caucasians (Dammerman et al 1993;Ordovas et al 1991;Shoulders et al 1996), Arabs (Tas 1989) and Japanese (Zeng et al 1995), and with elevated plasma apoCIII levels in healthy English (Shoulders et al 1991), Italian school children (Shoulders et al 1996) and Dutch Caucasians' spouses (Dallinga-Thie et al 1997).…”