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

Abstract

The frequencies of Type II (non-insulin-dependent) diabetes mellitus, atherosclerosis and components of -syndrome X, such as insulin resistance and dyslipidaemia, vary considerably among ethnic groups. South Asians and black subjects have a higher prevalence of Type II diabetes and hypertension than white subjects. Black subjects, however, have a favourable lipid profile and thus a lower risk of coronary heart disease (CHD) than South Asians, who have a highrisk lipid profile and consequently a high prevalence of CHD [1±3]. Risk factors such as obesity and smoking also vary widely between ethnic groups: black women have a high prevalence of obesity while white subjects have a high prevalence of smoking [1]. Some of these differences in disease susceptibility might depend on cultural inheritance or on the environment, but genetic variation could also play a part.We have previously shown that a polymorphism in the insulin response element (IRE) of the apolipoprotein CIII (ApoCIII) gene promoter (±482C > T) Diabetologia (2001) AbstractAims/hypothesis. The apolipoprotein C3±482C > T variant modulates insulin and glucose concentrations after an oral glucose tolerance test (OGTT) in young healthy white men. We evaluated the effect of this variant in different ethnic groups with different rates of Type II (non-insulin-dependent) diabetes mellitus and coronary heart disease. Methods. We investigated the ±482C > T in a population-based cross-sectional study of white subjects (n = 462), South Asians (n = 442) and subjects of West African and Afro-Caribbean origin (n = 462), whose OGTT and fasting plasma triglyceride concentrations had been measured. Results. The ±482T allele frequency differed between the three groups: 0.25 (95 % CI 0.22±0.28) in white subjects, 0.44 (0.41±0.47) in South Asians and 0.71 (0.68±0.74) in black subjects (p < 0.0001). A positive association was found between body mass index and genotype in black women (p = 0.009) and in black men (p = 0.056) but not in white subjects or South Asians. Associations between ±482C > T and fasting insulin were found in white subjects, where ±482T allele carriers had higher concentrations (adjusted for age and sex, p = 0.007, also including smoking and body mass index, p = 0.038). Higher triglyceride concentrations (p = 0.004 and p = 0.007 in the two models) but not glucose concentrations were also associated with ±482C > T. In black subjects, decreased fasting insulin (p = 0.04) and fasting glucose (p = 0.004) were associated with ±482C > T. No relation was observed between genotype and any post-load measures. Conclusions/interpretation. Allele frequencies of the ±482C > T and associations with insulin, glucose and triglyceride concentrations vary considerably among ethnic groups. Although the results are consistent among white subjects across different studies, the associations among black subjects and South Asians differ. [Diabetologia (2001) 44: 245±248]

Frequencies of the T-455C and C-482T apoCIII gene polymorphisms in different South African population groups and their relationship to fasting serum triglyceride levels

“…That study gave very similar allelic frequencies for the C-482T polymorphism to those described in the current study however, the T-455C polymorphism was not analysed. (18) The allelic frequencies observed for the C-482T and T-455C polymorphisms for the European population in the current paper are also very similar to those reported previously for a Dutch population. (19) The two apoCIII gene promoter polymorphisms examined in this study lie within an insulin response element (IRE).…”

“…This fi nding is supported by data from a previous study by Waterworth et al (18) demonstrating that the allelic frequencies of the C-482T polymorphism differs between European, South-Asian and Afro-Caribbean/West…”

“…(5,11,13,18) However, there are studies that failed to show such associations. (24)(25)(26) The present study was also unable to fi nd differences in allelic frequencies at either locus between hypertriglyceridaemic and control subjects, again sug-…”

“…However, one study has shown that the apoCIII C-482T polymorphism has no relationship with BMI in European and South Asian subjects but does in a mixed group of Afro-Caribbean/West African subjects where BMI was higher in the presence of the -482T allele. (18) However, adjusting for BMI had minimal effects on the statistical outcomes for the relationship between the C-482T genotype and triglyceride levels, in any of the 3 ethnic groups. (18) The current study was unable to show associations between either apoCIII polymorphism and lipid levels.…”

Age-Related Effects of Genetic Variation on Lipid Levels: The Columbia University BioMarkers Study

“…We previously identified a highly significant frequency difference of the APOC3 Ϫ482CϾT between whites, Asians from the Indian subcontinent, and Africans, all living in South London, suggesting that this polymorphism shows a high degree of ethnic variation. 54 Similarly, ethnic frequency differences have been reported for the HL Ϫ480CϾT 55 For the HL Ϫ480CϾT, the effect on plasma HDL cholesterol was modest in the children with the rare allele associated with higher levels. In the adults, a significant but modest effect was seen on plasma TG levels and LDL cholesterol levels; carriers of the rare T allele had significantly higher levels than individuals who were homozygous for the HL Ϫ480 T allele.…”