Association of anAPOC3promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons

✍ Scribed by M. van Hoek; T. W. van Herpt; A. Dehghan; A. Hofman; A. G. Lieverse; C. M. van Duijn; J. C. M. Witteman; E. J. G. Sijbrands

• Publisher: Springer
• Year: 2011
• Tongue: English
• Weight: 153 KB
• Volume: 54
• Category: Article
• ISSN: 0012-186X
• DOI: 10.1007/s00125-011-2092-x

✦ Synopsis

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.