Exploration of single nucleotide polymorphisms (SNPs) within four genes involved with cardiac function and their association with sudden unexplained death.

Tierney Mullaney, Jane Pritchard, Mark Payton, Jun Fu, Shen Di, Robert Allen


Seventeen blood samples obtained at autopsy from individuals determined to have died from cardiac-related causes were subjected to DNA analysis to explore possible associations of single nucleotide variations in a panel of 4 genes known to be involved in cardiac function. DNA was extracted from the autopsy samples as well as from a panel of 49 unaffected, presumably normal individuals and was subjected to nucleotide sequencing at selected sites within the EYA4, MYH6, TNNI3, and NEXN genes known to be involved with cardiac function. A total of 5 single nucleotide polymorphisms (SNPs) in the 4 genes (2 SNPs within the EYA4 gene) were interrogated through DNA sequencing. Each SNP site harbored either a nucleotide considered to represent a wild type allele, or a nucleotide considered a variant capable of impacting the normal functioning of the product of the gene. The purpose of the study was to determine if a greater number of variant alleles exist in the samples from the Medical Examiner than in the general population, and whether any particular SNP phenotypes or combinations of phenotypes are significantly linked to cardiac-related death. Results from the analysis showed individuals who died from cardiac-related causes had a significantly higher frequency of variant SNPs within the four genes than did the normal group. Moreover, particular combinations of variant nucleotide phenotypes were associated with cardiac death among the cohort of samples provided by the Medical Examiner. Our results support the notion that death from cardiac-related causes can result from single nucleotide polymorphisms that, by themselves are not lethal, but result in less than optimal performance of their respective gene products. Variant SNPs in several genes may collectively compromise cardiac function sufficiently to critically elevate the risk of death when elevated demands are placed on cardiac function.


Single nucleotide polymorphism; cardiac-related death, Cardiomyopathy, Genotyping

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