Association of intronic single-nucleotide polymorphisms in the EMILIN1 gene with essential hypertension in a Chinese population

• Published in: Journal of human hypertension Vol. 26; no. 9; pp. 553 - 561
• Main Authors: Oh, V M S, Chua, B-M, Heng, C-K, Yeo, S-B, Yim, O-S, Yap, E P H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 631/208/726/649; 692/699/75/243; 692/700/478/174; Adult; Alleles; Arterial hypertension. Arterial hypotension; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Care and treatment; Case-Control Studies; Chinese; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Demographic aspects; Diabetes mellitus; Elastin; Elastin microfibril interface located protein; Epidemiology; Essential Hypertension; Exons; Female; Gene Frequency; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Health Administration; Health aspects; Humans; Hypertension; Hypertension - genetics; Identification and classification; Introns; Introns - genetics; Linkage Disequilibrium; Male; Medical sciences; Medicine; Medicine & Public Health; Membrane Glycoproteins - genetics; Microfibrils; Middle Aged; original-article; Polymorphism, Single Nucleotide; Population studies; Public Health; Risk factors; Risk groups; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Singapore; essential hypertension; blood pressure; Chinese; haplotype; elastin microfibril interfacer 1; genetic polymorphism; Hypertension; Elastin; Cardiovascular disease; Arterial pressure; Blood pressure; Single nucleotide polymorphism; Haplotype
• ISSN: 0950-9240; 1476-5527; 1476-5527
• DOI: 10.1038/jhh.2011.68

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.