2011-06-01
Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons
Publication
Publication
Diabetologia: clinical and experimental diabetes and metabolism , Volume 54 - Issue 6 p. 1360- 1367
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.
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| , , , , | |
| doi.org/10.1007/s00125-011-2092-x, hdl.handle.net/1765/23803 | |
| Diabetologia: clinical and experimental diabetes and metabolism | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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van Hoek, M., van Herpt, T., Dehghan, A., Hofman, A., Lieverse, A., van Duijn, C., … Sijbrands, E. (2011). Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons. Diabetologia: clinical and experimental diabetes and metabolism, 54(6), 1360–1367. doi:10.1007/s00125-011-2092-x |
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