Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Sci Rep. 2019 Nov 1;9(1):15818. doi: 10.1038/s41598-019-48899-3.
The association between several Single Nucleotide Polymorphisms (SNPs) within the transcription factor 7-like 2 (TCF7L2) gene and Type 2 Diabetes (T2D) as well as additional T2D-related traits is well established. Since alteration in total and regional brain volumes are consistent findings among T2D individuals, we studied the association of four T2D susceptibility SNPS within TCF7L2 (rs7901695, rs7903146, rs11196205, and rs12255372) with volumes of white matter hyperintensities (WMH), gray matter, and regional volumes of amygdala and hippocampus obtained from structural MRI among 191 T2D elderly Jewish individuals. Under recessive genetic model (controlling for age, sex and intracranial volume), we found that for all four SNPs, carriers of two copies of the T2D risk allele (homozygous genotype) had significantly smaller amygdalar volume: rs7901695- CC genotype vs. CT + TT genotypes, p = 0.002; rs7903146-TT vs. TC + CC, p = 0.003; rs11196205- CC vs. CG + GG, p = 0.0003; and rs12255372- TT vs. TG + GG, p = 0.003. Adjusting also for T2D-related covariates, body mass index (BMI), and ancestry did not change the results substantively (rs7901695, p = 0.003; rs7903146, p = 0.005; rs11196205, p = 0.001; and rs12255372, p = 0.005). Conditional analysis demonstrated that only rs11196205 was independently associated with amygdalar volume at a significant level. Separate analysis of left and right amygdala revealed stronger results for left amygdalar volume. Taken together, we report association of TCF7L2 SNPs with amygdalar volume among T2D elderly Jewish patients. Further studies in other populations are required to support these findings and reach more definitive conclusions.
转录因子 7 样 2（TCF7L2）基因内的几个单核苷酸多态性（SNPs）与 2 型糖尿病（T2D）以及其他 T2D 相关特征之间的关联已得到充分证实。由于 T2D 个体的总脑体积和区域脑体积变化是一致的发现，我们研究了 TCF7L2 内四个 T2D 易感性 SNP（rs7901695、rs7903146、rs11196205 和 rs12255372）与 191 名老年犹太 T2D 个体结构 MRI 获得的白质高信号（WMH）、灰质和杏仁核和海马体区域体积之间的关联。在隐性遗传模型（控制年龄、性别和颅内体积）下，我们发现对于所有四个 SNP，两个 T2D 风险等位基因（纯合基因型）的携带者的杏仁核体积明显更小：rs7901695-CC 基因型与 CT+TT 基因型相比，p=0.002；rs7903146-TT 与 TC+CC 相比，p=0.003；rs11196205-CC 与 CG+GG 相比，p=0.0003；rs12255372-TT 与 TG+GG 相比，p=0.003。即使调整了与 T2D 相关的协变量（体重指数 BMI 和祖源），结果也没有实质性变化（rs7901695，p=0.003；rs7903146，p=0.005；rs11196205，p=0.001；rs12255372，p=0.005）。条件分析表明，只有 rs11196205 与杏仁核体积的关联在显著水平上是独立的。对左、右杏仁核的单独分析显示，左杏仁核体积的结果更强。总之，我们报告了 TCF7L2 SNP 与老年犹太 T2D 患者杏仁核体积之间的关联。需要在其他人群中进行进一步的研究，以支持这些发现并得出更明确的结论。
