Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
J Hum Hypertens. 2012 Sep;26(9):553-61. doi: 10.1038/jhh.2011.68. Epub 2011 Jul 14.
Studies in mice suggest that the elastin microfibril interfacer-1 gene (EMILIN1), the gene encoding elastin microfibril interfacer-1 protein, contributes to the pathogenesis of essential hypertension (EH) in humans. EMILIN1 in part maintains elastic fibres in vessel walls, and hence peripheral arterial compliance. In a case-control study, we assessed 942 non-obese non-diabetic Chinese, comprising 467 patients with EH and 475 normotensive control subjects (166 without, and 309 with, family history of hypertension in first-degree relatives (FHH)). Hypertension in first-degree relatives occurred in 88%, 65% and 0% of cases, all controls and controls without FHH, respectively. We scanned for single-nucleotide polymorphisms (SNPs) and genotyped them in the EMILIN1 gene using high-resolution melt-curve analysis. No exonic variants were detected. We assessed the association of SNPs and their haplotypes with EH. Three SNPs in introns 1 and 5 (rs2289360, rs2011616 and rs7424556) were in strong pair-wise linkage disequilibrium (r(2)>0.89). All three SNPs were significantly associated with hypertension. Genotypic frequencies at the three SNPs differed significantly between cases and only those controls without FHH. Healthy controls with FHH should be excluded to increase the odds of detecting association. All the G alleles of rs2289360 (odds ratio = 1.69, P = 0.010), rs2011616 (odds ratio = 1.52, P = 0.038) and rs7424556 (odds ratio = 1.59, P = 0.023) were high-risk alleles in the recessive genetic model. We observed significant overall haplotypic association with EH (empirical P = 0.0072); GGG is a risk haplotype (P = 0.043). The overall results support EMILIN1 as a candidate gene for human EH.
在小鼠中的研究表明，弹性微纤维界面蛋白 1 基因（EMILIN1），编码弹性微纤维界面蛋白 1 蛋白的基因，有助于人类原发性高血压（EH）的发病机制。EMILIN1 在一定程度上维持血管壁中的弹性纤维，从而维持外周动脉顺应性。在一项病例对照研究中，我们评估了 942 名非肥胖非糖尿病的中国人，包括 467 名 EH 患者和 475 名血压正常的对照受试者（166 名无一级亲属高血压家族史，309 名有一级亲属高血压家族史）。一级亲属中高血压的发生率分别为 88%、65%和 0%，分别为所有对照和无一级亲属高血压家族史的对照。我们使用高分辨率熔解曲线分析在 EMILIN1 基因中扫描单核苷酸多态性（SNP）并对其进行基因分型。未检测到外显子变异。我们评估了 SNP 及其单倍型与 EH 的关联。位于内含子 1 和 5 的三个 SNP（rs2289360、rs2011616 和 rs7424556）在强连锁不平衡（r(2)>0.89）。这三个 SNP 均与高血压显著相关。在病例和仅无一级亲属高血压家族史的对照中，三个 SNP 的基因型频率存在显著差异。应排除有一级亲属高血压家族史的健康对照者，以提高检测关联的可能性。rs2289360 的所有 G 等位基因（比值比=1.69，P=0.010）、rs2011616（比值比=1.52，P=0.038）和 rs7424556（比值比=1.59，P=0.023）在隐性遗传模型中均为高风险等位基因。我们观察到与 EH 有显著的总体单倍型关联（经验 P=0.0072）；GGG 是一个风险单倍型（P=0.043）。总体结果支持 EMILIN1 是人类 EH 的候选基因。
