Third Department of Internal Medicine, University of Fukui Faculty of Medical Sciences, 23-3, Matsuokashimoaizuki, Eiheiji, Fukui, 910-1193, Japan.
Department of Environmental and Preventive Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Sci Rep. 2020 Sep 30;10(1):16111. doi: 10.1038/s41598-020-73094-0.
The renin-angiotensin system (RAS) is important in the onset and course of cardiovascular, kidney, and metabolic disorders. Previous reports showed that the RAS blockade protects organs and suppress the development of type 2 diabetes mellitus. A novel component of the RAS, namely, chromosome 9 open reading frame 3 (C9orf3), was recently identified, however, its effects are unclear. We evaluated whether the genetic variant of C9orf3 is associated with morbidity of hypertension among subjects with type 2 diabetes. We enrolled 382 subjects with type 2 diabetes, 222 of whom were diagnosed with hypertension. Human leukocyte genomic DNA was isolated and a genetic variant was analyzed for a C/T variant of C9orf3 (rs4385527) via PCR analysis. The relationship between the genotype and hypertension morbidity among subjects with diabetes was examined. The proportion of the respective C9orf3 genetic variants were as follows 247 CC, 119 CT, and 16 TT. The risk of hypertension was determined to be 1.58, with a 95% confidence interval of 1.11-2.27. Moreover, the p value was 0.012 for allelic comparison and for Armitage's trend test, with the C allele identified as the risk factor. Consequently, hypertension was markedly associated with type 2 diabetes in subjects with the C9orf3 variant, exhibiting a nearly 1.6-fold increased risk. The C variant of a new component of the RAS, C9orf3 (rs4385527) might have a considerable impact on the pathogenesis of hypertension in diabetes.
肾素-血管紧张素系统（RAS）在心血管、肾脏和代谢紊乱的发生和过程中起重要作用。以前的报告表明，RAS 阻断剂可保护器官并抑制 2 型糖尿病的发展。最近发现了 RAS 的一个新组成部分，即染色体 9 开放阅读框 3（C9orf3），但其作用尚不清楚。我们评估了 C9orf3 的遗传变异是否与 2 型糖尿病患者高血压的发病率有关。我们招募了 382 名 2 型糖尿病患者，其中 222 名患有高血压。分离人类白细胞基因组 DNA，并通过 PCR 分析分析 C9orf3（rs4385527）的 C/T 变异。检查基因型与糖尿病患者高血压发病率之间的关系。各自 C9orf3 遗传变异的比例如下：247CC、119CT 和 16TT。高血压的风险被确定为 1.58，95%置信区间为 1.11-2.27。此外，等位基因比较和 Armitage 趋势检验的 p 值分别为 0.012 和 0.012，C 等位基因为危险因素。因此，C9orf3 变异的高血压与 2 型糖尿病显著相关，风险增加近 1.6 倍。RAS 的新组成部分 C9orf3（rs4385527）的 C 变体可能对糖尿病中高血压的发病机制有很大影响。
