Key result
The NPPA rs5065 variant was not significantly associated with overall stroke (OR 1.3), but demonstrated a significantly higher minor allele frequency in the cardioembolic stroke subtype compared to controls (adjusted p=0.002).
Why the study?
Are polymorphisms of the NPPA and NPPB genes associated with stroke in a Korean population?
Case-Control (n=941)
Yes
Are polymorphisms of the NPPA and NPPB genes associated with stroke in a Korean population?
Odds Ratio: 1.3 (95% CI 0.2–7.4)
Absolute Event Rate: 0.007% vs 0.006%
p-value: p=0.779
The nonsynonymous rs5065C variant of the NPPA gene is potentially associated with cardioembolic stroke in the Korean population.
Hypothesis-generating for NPPA variants in Korean cardioembolic stroke; prospective validation required before clinical consideration.
Atrial natriuretic peptide (ANP, also known as NPPA) and brain natriuretic peptide (BNP, also known as NPPB) have been determined as genetic factors for several diseases, including stroke and myocardial infarction, in human and rat models. To investigate the potential association between polymorphisms of the NPPA gene and stroke in a Korean population, nine single-nucleotide polymorphisms (SNPs) of NPPA and NPPB genes were genotyped in a total of 941 Korean subjects, including 674 stroke patients (109 hemorrhagic and 565 ischemic) and 267 unaffected controls. Genotype comparisons of the targeted alleles revealed that there were no significant associations between stroke patients and control subjects, or among hemorrhagic, ischemic, and control groups. However, in logistic analysis for Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of ischemic stroke, nonsynonymous rs5065 (STOP152Arg) and rs5067 in 3'UTR of NPPA, which were in complete linkage disequilibrium, showed significant associations with cardioembolic stroke. These two SNPs showed higher frequencies in cardioembolic stroke patients than those in controls and ischemic patients with small-vessel occlusion (p=0.002, adjusted p=0.02). It was also found that NPPA rs5065C allele in all of the Korean subjects existed as heterozygous compared with Caucasian and African populations. Although further replications in larger cardioembolic stroke subjects are required, our preliminary findings suggest that the nonsynonymous rs5065C of the NPPA gene, which could produce a new or dysfunctional transcript, is possibly associated with cardioembolism.
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Kim et al. (2012) conducted a case-control in Stroke (n=941). NPPA rs5065 variant vs. Unaffected controls was evaluated on Association of NPPA rs5065 variant with overall stroke (OR 1.3, 95% CI 0.2-7.4, p=0.779). The NPPA rs5065 variant was not significantly associated with overall stroke (OR 1.3), but demonstrated a significantly higher minor allele frequency in the cardioembolic stroke subtype compared to controls (adjusted p=0.002).
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