Johansson Lovisa E, Danielsson Pernilla, Norgren Svante, Marcus Claude, Ridderstråle Martin
Department of Clinical Sciences Malmö, Clinical Obesity, Lund University, CRC, UMAS, Ing 72, Hus 91, Plan 12, Malmö S-205 02, Sweden.
Int J Pediatr Obes. 2009;4(2):119-25. doi: 10.1080/17477160802263194.
The aim of this study was to investigate the role of two candidate gene polymorphisms for insulin resistance and lipid levels in obese children and adolescents.
Two markers of insulin resistance and lipid levels, Pro12Ala in peroxisome proliferator-activated receptor-gamma2 (PPARG) and G276T in adiponectin (ADIPOQ), were genotyped in 285 obese children and adolescents. As the apolipoprotein E (APOE) polymorphisms C112R and R158C are known to have a profound impact on lipid levels in both children and adults, results were adjusted for APOE genotype.
We found no association for PPARG or ADIPOQ polymorphisms with Body Mass Index (BMI), High Density Lipoprotein (HDL)-cholesterol, triglycerides or Insulin Resistance estimated by Homeostasis Model of Assessment (HOMA-IR). Wild type carriers of PPARG Pro12Ala (p<0.05), homozygous carriers of the variant allele of ADIPOQ G276T (p<0.001) and epsilon4 carriers of APOE (p<0.001) had higher total and low density lipoprotein (LDL)-cholesterol levels adjusted for age, gender, BMI and insulin sensitivity. A PPARG/ADIPOQ risk genotype combination was identified by analysis of covariance (ANCOVA) comparing all existing combinations. Carriers of PPARG Pro/Pro and ADIPOQ 276 T/T had higher total (5.0 [4.1-5.8] vs. 4.1 [3.6-4.6] mmol/l) and LDL-cholesterol levels (3.7 [2.9-4.5] vs. 3.0 [2.5-3.5] mmol/l) compared with carriers of other combinations (p<0.001). Importantly, the PPARG and ADIPOQ associations were unaffected when adjusting for APOE genotype.
Genetic variants in candidate genes for insulin resistance are associated with cholesterol levels in obese children and adolescents, and may offer additional information in the risk assessment of obese children.
本研究旨在调查两个候选基因多态性在肥胖儿童和青少年胰岛素抵抗及血脂水平中所起的作用。
对285名肥胖儿童和青少年进行过氧化物酶体增殖物激活受体γ2（PPARG）基因Pro12Ala及脂联素（ADIPOQ）基因G276T这两个胰岛素抵抗和血脂水平标志物的基因分型。由于已知载脂蛋白E（APOE）基因多态性C112R和R158C对儿童和成人的血脂水平均有深远影响，因此对结果按APOE基因型进行了校正。
我们发现PPARG或ADIPOQ基因多态性与体重指数（BMI）、高密度脂蛋白（HDL）胆固醇、甘油三酯或通过稳态模型评估（HOMA-IR）估算的胰岛素抵抗均无关联。校正年龄、性别、BMI和胰岛素敏感性后，PPARG Pro12Ala的野生型携带者（p<0.05）、ADIPOQ G276T变异等位基因的纯合子携带者（p<0.001）以及APOE的ε4携带者（p<0.001）的总胆固醇和低密度脂蛋白（LDL）胆固醇水平较高。通过协方差分析（ANCOVA）比较所有现有组合，确定了一种PPARG/ADIPOQ风险基因型组合。与其他组合的携带者相比，PPARG Pro/Pro和ADIPOQ 276 T/T的携带者总胆固醇水平更高（5.0 [4.1-5.8] mmol/l对4.1 [3.6-4.6] mmol/l），LDL胆固醇水平也更高（3.7 [2.9-4.5] mmol/l对3.0 [2.5-3.5] mmol/l）（p<0.001）。重要的是，校正APOE基因型后，PPARG和ADIPOQ的关联不受影响。
胰岛素抵抗候选基因中的遗传变异与肥胖儿童和青少年的胆固醇水平相关，可能为肥胖儿童的风险评估提供额外信息。
