Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Am J Hypertens. 2010 May;23(5):547-55. doi: 10.1038/ajh.2010.16. Epub 2010 Feb 25.
Elastin microfibril interfacer 1 (EMILIN-1) is a negative regulator of the transforming growth factor-beta (TGF-beta) signaling, which is involved in blood pressure (BP) homeostasis. Emilin1 knockout mice display elevated BP. The aim of the present study was to assess the association between the human EMILIN1 gene and essential hypertension (EH) using a haplotype-based case-control study.
A total of 287 EH patients and 253 age-matched controls were genotyped for the five single-nucleotide polymorphisms (SNPs) used as genetic markers for the human EMILIN1 gene (rs2289408, rs2289360, rs2011616, rs2304682, and rs4665947). Data were analyzed for three separate groups: the total subjects, men, and women.
For the total, the genotypic distribution of rs2289360, rs2011616, and rs2304682 differed significantly between control and EH (P = 0.010, P = 0.009, and P = 0.008, respectively). For the total and men, there were significant differences noted between the controls and the EH patients for both the dominant model (GG vs. AA+AG) (P = 0.006, P = 0.021, respectively), and the recessive model (AA vs. AG+GG) (P = 0.028, P = 0.038, respectively) of rs2011616. For the total and the men, logistic regression analysis indicated that the AG+GG genotype of rs2011616 was significantly higher in EH patients (P = 0.033, P = 0.043, respectively). The frequency of the G-G-T haplotype (established by rs2536512, rs2016116, rs17881426) was significantly higher in EH men (P = 0.007), and the G-A-T haplotype (established by rs2536512, rs2016116, rs17881426) was significantly higher in control men (P < 0.001).
We confirmed that rs2289360, rs2011616, and rs2304682 in the human EMILIN1 gene, as well as the haplotype constructed using rs2536512, rs2011616, and rs17881426 are useful genetic markers of EH in Japanese men.
弹性蛋白微纤维界面蛋白 1（EMILIN-1）是转化生长因子-β（TGF-β）信号的负调节剂，参与血压（BP）稳态。Elimin1 敲除小鼠显示血压升高。本研究旨在通过基于单体型的病例对照研究评估人类 EMILIN1 基因与原发性高血压（EH）之间的关联。
对 287 名 EH 患者和 253 名年龄匹配的对照进行了五个单核苷酸多态性（SNP）的基因分型，这些 SNP 用作人类 EMILIN1 基因（rs2289408、rs2289360、rs2011616、rs2304682 和 rs4665947）的遗传标记。数据分别对三个组进行分析：总人群、男性和女性。
在总人群中，rs2289360、rs2011616 和 rs2304682 的基因型分布在对照组和 EH 组之间有显著差异（P=0.010、P=0.009 和 P=0.008）。在总人群和男性中，rs2011616 的显性模型（GG 与 AA+AG）（P=0.006、P=0.021）和隐性模型（AA 与 AG+GG）（P=0.028、P=0.038）的对照组和 EH 患者之间存在显著差异。在总人群和男性中，逻辑回归分析表明 rs2011616 的 AG+GG 基因型在 EH 患者中显著升高（P=0.033、P=0.043）。EH 男性中 G-G-T 单体型（由 rs2536512、rs2016116 和 rs17881426 建立）的频率显著升高（P=0.007），而对照组男性中 G-A-T 单体型（由 rs2536512、rs2016116 和 rs17881426 建立）的频率显著升高（P<0.001）。
我们证实，人类 EMILIN1 基因中的 rs2289360、rs2011616 和 rs2304682 以及使用 rs2536512、rs2016116 和 rs17881426 构建的单体型是日本男性原发性高血压的有用遗传标记。
