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Diabetologia ; 54(6): 1360-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21373834

ABSTRACT

AIMS/HYPOTHESIS: An APOC3 promoter haplotype has been previously associated with type 1 diabetes. In this population-based study, we investigated whether APOC3 polymorphisms increase type 2 diabetes risk and need for insulin treatment in lean participants. METHODS: In the Rotterdam Study, a population-based prospective cohort (n = 7,983), Cox and logistic regression models were used to analyse the associations and interactive effects of APOC3 promoter variants (-482C > T, -455T > C) and BMI on type 2 diabetes risk and insulin treatment. Analyses were followed by replication in an independent case-control sample (1,817 cases, 2,292 controls) and meta-analysis. RESULTS: In lean participants, the -482T allele was associated with increased risk of prevalent and incident type 2 diabetes: OR -482CT 1.47 (95% CI 1.13-1.92), -482TT 1.40 (95% CI 0.83-2.35), p = 0.009 for trend; HR -482CT 1.35 (95% CI 0.96-1.89), -482TT 1.68 (95% CI 0.91-3.1), p = 0.03 for trend, respectively. These results were confirmed by replication. Meta-analysis was highly significant (-482T meta-analysis p = 1.1 × 10(-4)). A borderline significant interaction was observed for insulin use among participants with type 2 diabetes (-482CT*BMI p = 0.06, -455TC*BMI p = 0.02). CONCLUSIONS/INTERPRETATION: At a population-based level, the influence of APOC3 promoter variants on type 2 diabetes risk varies with the level of adiposity. Lean carriers of the -482T allele had increased type 2 diabetes risk, while such an effect was not observed in overweight participants. Conversely, in overweight participants the -455C allele seemed protective against type 2 diabetes. The interaction of the variants with need for insulin treatment may indicate beta cell involvement in lean participants. Our findings suggest overlap in the genetic backgrounds of type 1 diabetes and type 2 diabetes in lean patients.


Subject(s)
Apolipoprotein C-III/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease/genetics , Insulin/therapeutic use , Polymorphism, Single Nucleotide/genetics , Thinness/physiopathology , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Cohort Studies , Diabetes Mellitus, Type 2/physiopathology , Female , Haplotypes , Humans , Hypoglycemic Agents/therapeutic use , Logistic Models , Male , Middle Aged , Netherlands , Prevalence , Promoter Regions, Genetic/genetics , Prospective Studies , Risk Factors
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