{{Rsnum
|rsid=5065
|Gene=NPPA
|Chromosome=1
|position=11846011
|Orientation=plus
|ReferenceAllele=T
|MissenseAllele=C
|GMAF=0.1396
|Gene_s=NPPA,NPPA-AS1
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 72.6 | 26.5 | 0.9
| HCB | 99.3 | 0.7 | 0.0
| JPT | 97.3 | 2.7 | 0.0
| YRI | 33.3 | 45.6 | 21.1
| ASW | 36.8 | 52.6 | 10.5
| CHB | 99.3 | 0.7 | 0.0
| CHD | 99.1 | 0.9 | 0.0
| GIH | 76.2 | 21.8 | 2.0
| LWK | 44.5 | 45.5 | 10.0
| MEX | 82.8 | 13.8 | 3.4
| MKK | 46.2 | 44.2 | 9.6
| TSI | 78.4 | 21.6 | 0.0
| HapMapRevision=28
}}
[[rs5065]], also known as T2238C, is a SNP in the atrial natriuretic precursor A [[NPPA]] gene.

A large study has been conducted in which 42,418 hypertensive participants 55 or older were followed for several years while on one of four medications: a diuretic, a calcium antagonist, an angiotensin-converting enzyme inhibitor, or an alpha-blocker. The primary endpoint was either fatal [[heart disease]] or a heart attack.{{PMID|18212314}}

The blood pressure after six months of [[rs5065]](G;G) patients (note: genotype is in dbSNP orientation, not as published) was lower if the patients were treated with diuretics compared to other medications, with smaller variation seen for (A;A) genotypes. The authors noted that none of the findings retained statistical significance after correction for multiple comparisons, but since the trend held in five of seven outcomes, they felt the results were nonetheless worth reporting. 

In summary, [[rs5065]](G) allele carriers were better off (i.e. experienced more favorable cardiovascular disease outcomes) if treated with the diuretic (in this case, [[chlorthalidone]]), whereas [[rs5065]](A;A) carriers were better off if treated with the calcium channel blocker (in this case, [[amlodipine]]).

{{ neighbor
| rsid = 5067
| distance = 87
}}

{{PharmGKB
|RSID=rs5065
|Name_s=
|Gene_s=NPPA, CLCN6
|Feature=Exon/NonSyn, NA
|Evidence=PubMed ID:20026756
|Annotation=The minor allele of this SNP(G on the + strand) was associated with decreased asthma susceptibility. This PMID is a correction to the original (PMID: 19264973); details of the study are in that article.
|Drugs=
|Drug Classes=
|Diseases=Asthma
|Curation Level=Curated
|PharmGKB Accession ID=PA165111692
}}

{{PMID Auto
|PMID=20543198
|Title=Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation
|OA=1
}}

{{PharmGKB
|RSID=rs5065
|Name_s=NPPA:T2238C
|Gene_s=NPPA, CLCN6
|Feature=Exon/NonSyn, NA
|Evidence=PubMed ID:18212314
|Annotation=This variant has been associated with modification of antihypertensive medication effects on blood pressure and cardiovascular disease.
|Drugs=amlodipine; chlorthalidone; doxazosin; lisinopril
|Drug Classes=
|Diseases=Cardiovascular Diseases; Coronary Disease; Stroke
|Curation Level=Curated
|PharmGKB Accession ID=PA161614192
}}

{{PMID Auto
|PMID=22575314
|Title=Influence of rs5065 Atrial Natriuretic Peptide Gene Variant on Coronary Artery Disease.
}}

{{PMID Auto
|PMID=17984371
|Title=Natriuretic peptide precursor a gene polymorphisms and risk of blood pressure progression and incident hypertension.
}}

{{PMID Auto
|PMID=18294255
|Title=A polymorphism in the NPPA gene associates with asthma.
}}

{{PMID Auto
|PMID=18513389
|Title=New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.
|OA=1
}}

{{PMID Auto
|PMID=19131662
|Title=A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
|OA=1
}}

{{PMID Auto
|PMID=19200524
|Title=A genome-wide survey of the prevalence and evolutionary forces acting on human nonsense SNPs.
|OA=1
}}

{{PMID Auto
|PMID=19263529
|Title=Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
|OA=1
}}

{{PMID Auto
|PMID=19326473
|Title=Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting.
|OA=1
}}

{{PMID Auto
|PMID=19330901
|Title=Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19559392
|Title=A candidate gene association study of 77 polymorphisms in migraine.
|OA=1
}}

{{PMID Auto
|PMID=20031578
|Title=Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=21273288
|Title=Genome-wide association analysis and fine mapping of NT-proBNP level provide novel insight into the role of the MTHFR-CLCN6-NPPA-NPPB gene cluster.
|OA=1
}}

{{PMID Auto
|PMID=21276798
|Title=Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes.
}}

{{PMID Auto
|PMID=22170009
|Title=Association of 2238T>C polymorphism of the atrial natriuretic peptide gene with coronary artery disease in Afro-Caribbeans with type 2 diabetes.
}}

{{PMID Auto
|PMID=22388798
|Title=Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment: the GenHAT study.
|OA=1
}}

{{GET Evidence
|gene=NPPA
|aa_change=Stop152Arg
|aa_change_short=X152R
|impact=not reviewed
|qualified_impact=Insufficiently evaluated not reviewed
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs5065
|overall_frequency_n=2591
|overall_frequency_d=10758
|overall_frequency=0.240844
|n_genomes=19
|n_genomes_annotated=0
|n_haplomes=23
|n_articles=0
|n_articles_annotated=0
|nblosum100=4
|autoscore=0
|webscore=N
}}

{{PMID Auto
|PMID=24041948
|Title=Atrial Natriuretic Peptide Genetic Variant rs5065 and Risk for Cardiovascular Disease in the General Community: A 9-Year Follow-Up Study
}}

{{PMID Auto
|PMID=24093000
|Title=Atrial Natriuretic Peptide Single Nucleotide Polymorphisms in Patients with Nonfamilial Structural Atrial Fibrillation
|OA=1
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}