Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, WA, Australia.
BMC Med Genet. 2010 Oct 8;11:140. doi: 10.1186/1471-2350-11-140.
Variation in the effects of genetic variants on physiological traits over time or with age may alter the trajectories of these traits. However, few studies have investigated this possibility for variants associated with type 2 diabetes or obesity, and these show little consensus. We aimed to characterise the possible longitudinal associations of common diabetes-susceptibility variants in the KCNJ11, PPARG, TCF7L2, IGF2BP2, CDKAL1, SLC30A8 and HHEX gene loci, with fasting glucose level; and of an obesity-associated variant in the FTO gene, with body mass index (BMI).
The study analysed data from the Busselton Health Study (n = 4,554). Cross-sectional association analyses included family data and used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models.
In cross-sectional analyses, we observed associations of the T allele at the IGF2BP2 single nucleotide polymorphism (SNP) rs4402960 with raised fasting glucose (p = 0.045), and the A allele at the FTO SNP rs9939609 with raised BMI (p = 0.003). Longitudinal analyses showed no significant associations between SNPs and changes in fasting glucose or BMI in the same individuals, either over mean follow-up times of 18.7 and 21.8 years respectively, or with age during adulthood.
There was no indication that the effects of common type 2 diabetes variants on fasting glucose varied with age during adulthood or over time.
遗传变异对生理特征的影响随时间或年龄的变化而变化，可能会改变这些特征的轨迹。然而，很少有研究调查与 2 型糖尿病或肥胖相关的变异在这方面的可能性，而且这些研究结果也没有达成共识。我们旨在描述 KCNJ11、PPARG、TCF7L2、IGF2BP2、CDKAL1、SLC30A8 和 HHEX 基因座中常见的糖尿病易感性变异与空腹血糖水平之间的可能纵向关联；以及 FTO 基因中与体重指数（BMI）相关的肥胖相关变异。
该研究分析了 Busselton 健康研究（n=4554）的数据。横断面关联分析包括家族数据，并使用总关联检验。对无关联参与者数据（n=2864）的纵向关联分析采用线性混合效应模型。
在横断面分析中，我们观察到 IGF2BP2 单核苷酸多态性（SNP）rs4402960 的 T 等位基因与空腹血糖升高（p=0.045）有关，FTO SNP rs9939609 的 A 等位基因与 BMI 升高（p=0.003）有关。纵向分析显示，在相同个体中，SNP 与空腹血糖或 BMI 的变化之间没有显著关联，无论是平均随访时间分别为 18.7 年和 21.8 年，还是成年期间的年龄。
没有迹象表明常见 2 型糖尿病变异对成年期空腹血糖的影响随时间或年龄而变化。
