Webster R J, Warrington N M, Weedon M N, Hattersley A T, McCaskie P A, Beilby J P, Palmer L J, Frayling T M
Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, B Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia.
Diabetologia. 2009 Jan;52(1):106-14. doi: 10.1007/s00125-008-1175-9. Epub 2008 Nov 19.
AIMS/HYPOTHESIS: Common genetic variants influence plasma triacylglycerol, HDL-cholesterol (HDL-C) and glucose levels in cross-sectional studies. However, the longitudinal effects of these established variants have not been studied. Our aim was to examine the longitudinal associations of four such variants in the apolipoprotein A-V (APOA5), lipoprotein lipase (LPL), and glucokinase (GCK) genes with fasting glucose or lipid levels.
The individuals analysed were participants in the Busselton Health Survey (n = 4,554). Cross-sectional analyses of family data used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models.
The findings of cross-sectional association analyses replicated those of previous studies. We observed associations of the G and C alleles at the APOA5 single nucleotide polymorphisms (SNPs) rs662799 and rs3135506 with raised triacylglycerol levels (p = 0.0003 and p < 0.0001, respectively), the 447X allele at the LPL SNP rs328 with reduced triacylglycerol levels (p = 0.0004) and raised HDL-C levels (p = 0.0004), and the A allele of the GCK SNP rs1799884 with raised fasting glucose level (p = 0.015). Longitudinal association analyses showed that most of these associations did not change in the same individuals over an average follow-up time of 17.4 years, though there was some evidence that the association of the 447X allele of rs328 with raised HDL-C level significantly increased with age (p = 0.01), and that the association of the C allele of rs3135506 with raised triacylglycerol level significantly increased over time (p = 0.0007).
CONCLUSIONS/INTERPRETATION: The current study suggests that the effects of established gene variants on lipid and glucose traits do not tend to alter with age during adulthood or over time.
目的/假设：在横断面研究中，常见基因变异会影响血浆甘油三酯、高密度脂蛋白胆固醇（HDL-C）和血糖水平。然而，这些已确定变异的纵向影响尚未得到研究。我们的目的是研究载脂蛋白A-V（APOA5）、脂蛋白脂肪酶（LPL）和葡萄糖激酶（GCK）基因中的四种此类变异与空腹血糖或血脂水平的纵向关联。
分析的个体为巴瑟尔顿健康调查的参与者（n = 4554）。家庭数据的横断面分析使用全关联检验。无关参与者数据（n = 2864）的纵向关联分析使用线性混合效应模型。
横断面关联分析的结果重复了先前研究的结果。我们观察到，APOA5单核苷酸多态性（SNP）rs662799和rs3135506处的G和C等位基因与甘油三酯水平升高相关（分别为p = 0.0003和p < 0.0001），LPL SNP rs328处的447X等位基因与甘油三酯水平降低（p = 0.0004）和HDL-C水平升高（p = 0.0004）相关，GCK SNP rs1799884的A等位基因与空腹血糖水平升高相关（p = 0.015）。纵向关联分析表明，在平均17.4年的随访时间内，这些关联在同一人群中大多没有变化，不过有证据表明，rs328的447X等位基因与HDL-C水平升高的关联随年龄显著增加（p = 0.01），rs3135506的C等位基因与甘油三酯水平升高的关联随时间显著增加（p = 0.0007）。
结论/解读：当前研究表明，已确定的基因变异对脂质和血糖特征的影响在成年期或随时间推移不会随年龄而改变。
