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Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population

Glorioso, Nicola and Herrera, Victoria L. M. and Didishvili, Tamara and Ortu, Maria Francesca and Zaninello, Roberta and Fresu, Giovanni and Argiolas, Giuseppe and Troffa, Chiara and Ruiz-Opazo, Nelson (2013) Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population. PLoS One, Vol. 8 (10), e77562. eISSN 1932-6203. Article.

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DOI: 10.1371/journal.pone.0077562

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Abstract

Coronary artery disease, heart failure, fatal arrhythmias, stroke, and renal disease are the most common causes of mortality for humans, and essential hypertension remains a major risk factor. Elucidation of susceptibility loci for essential hypertension has been difficult because of its complex, multifactorial nature involving genetic, environmental, and sex- and age-dependent nature. We investigated whether the 11p15.5 region syntenic to rat chromosome 1 region containing multiple blood pressure quantitative trait loci (QTL) detected in Dahl rat intercrosses harbors polymorphisms that contribute to susceptibility/resistance to essential hypertension in a Sardinian population. Initial testing performed using microsatellite markers spanning 18 Mb of 11p15.5 detected a strong association between D11S1318 (at 2.1 Mb, P = 0.004) and D11S1346 (at 10.6 Mb, P = 0.00000004), suggesting that loci in close proximity to these markers may contribute to susceptibility in our Sardinian cohort. NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR), and adrenomedullin (ADM) are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs) within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort. Upon sex stratification, we detected one NLRP6/AVR SNP associated with decreased susceptibility to hypertension in males (rs7948797G, P = 0.029; OR = 0.73 [0.57-0.94]). For ADM, sex-specific analysis showed a significant association between rs4444073C, with increased susceptibility to essential hypertension only in the male population (P = 0.006; OR = 1.44 [1.13-1.84]). Our results revealed an association between NLRP6/AVR and ADM loci with male essential hypertension, suggesting the existence of sex-specific NLRP6/AVR and ADM variants affecting male susceptibility to essential hypertension.

Item Type:Article
ID Code:9655
Status:Published
Refereed:Yes
Uncontrolled Keywords:NLRP6/AVR, ADM loci, hypertension, Sardinia
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Chirurgiche, Microchirurgiche e Mediche
002 Altri enti e centri di ricerca del Nord Sardegna > AOU -Azienda Ospedaliero Universitaria, Sassari
Publisher:Public Library of Science
eISSN:1932-6203
Copyright Holders:© Glorioso et al.
Deposited On:03 Mar 2014 10:28

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