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Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation.

ABSTRACT: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important cause of morbidity and mortality. A genetic mutation in the NPPA gene, which encodes the atrial natriuretic peptide, has been identified as the putative causative factor in a family with an autosomal dominant pattern of inheritance for AF. Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously implicated in conditions associated with AF, including stroke and hypertension. Recently, the rs5063 SNP has been reported to confer an increased risk of AF development in a Chinese population. We sought to examine the associations of both rs5063 and rs5065 with AF in two separate North American cohorts of European ancestry.Patients with early-onset AF, along with healthy controls, were recruited at the University of Ottawa Heart Institute (UOHI) and the Massachusetts General Hospital (MGH). Study participants were genotyped for rs5063 and rs5065 using a combination of restriction fragment length polymorphism analysis and DNA microarrays. The study genotyped a total of 620 AF cases and 2446 healthy controls. The UOHI arm of the study identified an odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.42-1.24] for rs5063, whereas an OR of 1.33 (95% CI: 0.80-2.21) was observed in the MGH arm. The combined OR approximated unity (OR 0.99; 95% CI: 0.54-1.80). Analysis of rs5065 revealed an OR of 1.12 (95% CI: 0.84-1.48) in UOHI, 1.08 (95% CI 0.80-1.45) in MGH, and 1.10 (95% CI 0.90-1.35) when combined.Common non-synonymous genetic variants within NPPA in these two large North American cohorts of European ancestry are not associated with the development of AF.

SUBMITTER: Roberts JD

PROVIDER: S-EPMC2910603 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation.

Roberts Jason D JD Davies Robert W RW Lubitz Steven A SA Thibodeau Isabelle L IL Nery Pablo B PB Birnie David H DH Benjamin Emelia J EJ Lemery Robert R Ellinor Patrick T PT Gollob Michael H MH

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 20100612 8

<h4>Aims</h4>Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important cause of morbidity and mortality. A genetic mutation in the NPPA gene, which encodes the atrial natriuretic peptide, has been identified as the putative causative factor in a family with an autosomal dominant pattern of inheritance for AF. Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously impl ...[more]

PMID: 20543198

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Project description:BackgroundSeveral non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia.MethodsWe examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.ResultsPAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.ConclusionHigher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.

Dataset Information

Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation.

Publications

Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation.

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