Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
Diabetologia. 2011 Jun;54(6):1360-7. doi: 10.1007/s00125-011-2092-x. Epub 2011 Mar 4.
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.
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.
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 (-482CTBMI p = 0.06, -455TCBMI 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.
目的/假设：先前有研究发现 APOC3 启动子单倍型与 1 型糖尿病有关。在这项基于人群的研究中，我们研究了 APOC3 多态性是否会增加瘦体型参与者 2 型糖尿病的发病风险和胰岛素治疗需求。
在鹿特丹研究中，这是一项基于人群的前瞻性队列研究（n=7983），使用 Cox 和逻辑回归模型分析 APOC3 启动子变异（-482C>T、-455T>C）与 BMI 对 2 型糖尿病发病风险和胰岛素治疗的关联及交互作用。在一项独立的病例对照样本（1817 例病例，2292 例对照）中进行了验证，并进行了荟萃分析。
在瘦体型参与者中，-482T 等位基因与现患和新发 2 型糖尿病的风险增加相关：OR-482CT 为 1.47（95%CI 1.13-1.92），-482TT 为 1.40（95%CI 0.83-2.35），p=0.009 趋势；HR-482CT 为 1.35（95%CI 0.96-1.89），-482TT 为 1.68（95%CI 0.91-3.1），p=0.03 趋势，分别。这些结果在验证中得到了证实。荟萃分析结果高度显著（-482T 荟萃分析 p=1.1×10（-4））。在 2 型糖尿病患者中，观察到胰岛素使用存在边缘显著的交互作用（-482CTBMI p=0.06，-455TCBMI p=0.02）。
结论/解释：在人群水平上，APOC3 启动子变异对 2 型糖尿病风险的影响随肥胖程度而变化。携带-482T 等位基因的瘦体型参与者发生 2 型糖尿病的风险增加，而超重参与者则没有这种影响。相反，在超重参与者中，-455C 等位基因似乎对 2 型糖尿病具有保护作用。变异与胰岛素治疗需求的相互作用可能表明在瘦体型参与者中β细胞参与其中。我们的研究结果表明，在瘦体型患者中，1 型糖尿病和 2 型糖尿病的遗传背景存在重叠。
