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

Journal of Human Hypertension volume 26, pages 553–561 (2012)Cite this article

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Abstract

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 (r2>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.

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Acknowledgements

We thank Linda Gan and Rita Yong for their help in the Molecular Genetics Laboratory of the Defence Medical & Environmental Research Institute, DSO Labs, Singapore and Bernadette GC Er for expert help in subject recruitment. We also thank Nicole PS Choa for help in manuscript preparation. The study was mainly supported by the National Medical Research Council, Singapore (grant no. NMRC/1067/2006) (BMC, BGCE). Other funding sources were Yong Loo Lin School of Medicine, National University of Singapore (VMSO), Shaw Foundation and Lee Foundation (BMC, BGCE), Singapore Heart Foundation (grant no. R-172-000-143-593) (BMC, BGCE), National Healthcare Group (R-172-000-146-490) (BMC, BGCE), the National University Hospital Patient Care Research Fund (grant no. R-172-000-139-592) (BMC, BGCE) and the Defence Science & Technology Agency, Singapore (EPHY).

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Authors and Affiliations

  1. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    V M S Oh, B-M Chua & S-B Yeo

  2. Department of Paediatrics, National University of Singapore, Singapore

    C-K Heng & O-S Yim

  3. Defence Medical & Environmental Research Institute, DSO National Labs, Singapore

    E P H Yap

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  1. V M S Oh
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Correspondence to V M S Oh.

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Oh, V., Chua, BM., Heng, CK. et al. Association of intronic single-nucleotide polymorphisms in the EMILIN1 gene with essential hypertension in a Chinese population. J Hum Hypertens 26, 553–561 (2012). https://doi.org/10.1038/jhh.2011.68

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