Key result
The SNP rs4952632[G] near the SLC8A1 gene was associated with a 2.325-ms longer PR interval per minor allele copy (95% CI 1.693-2.957; P=5.598×10^-13).
Observational (n=2,994)
Yes
Mean Difference: 2.325 (95% CI 1.693–2.957)
p-value: p=5.598 × 10(-13)
Identified a novel genetic association between SNP rs4952632[G] near the SLC8A1 gene and prolonged PR interval in East Asian populations, supporting the role of the sodium-calcium exchanger in cardiac conduction.
Supports SLC8A1 role in conduction; extends European data to East Asians but remains hypothesis-generating.
Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models.
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Sano et al. (2014) conducted an observational in Healthy volunteers (n=2,994). SNP rs4952632[G] (near SLC8A1) vs. Reference allele was evaluated on PR interval (MD 2.325, 95% CI 1.693-2.957, p=5.598 × 10(-13)). The SNP rs4952632[G] near the SLC8A1 gene was associated with a 2.325-ms longer PR interval per minor allele copy (95% CI 1.693-2.957; P=5.598×10^-13).
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