Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene

Antontseva, E.V.; Matveeva, M.Y.; Bondar, N.P.; Kashina, E.V.; Leberfarb, E.Y.; Bryzgalov, L.O.; Gervas, P.A.; Ponomareva, A.A.; Cherdyntseva, N.V.; Orlov, Y.L.; Merkulova, T.I.

Авторы: Antontseva Elena V., Matveeva Marina Yu, Bondar Natalia P., Kashina Elena V., Leberfarb Elena Yu, Bryzgalov Leonid O., Gervas Polina A., Ponomareva Anastasia A., Cherdyntseva Nadezhda V., Orlov Yury L., Merkulova Tatiana I.
Журнал: Journal of Biosciences
Том: 40
Номер: 5
Год издания: 2015
Издательство: Indian Academy of Sciences
Местоположение издательства: India
Первая страница: 873
Последняя страница: 883
DOI: 10.1007/s12038-015-9567-8
Аннотация: There are two regulatory single nucleotide polymorphisms (rSNPs) at the beginning of the second intron of the mouse K-ras gene that are strongly associated with lung cancer susceptibility. We performed functional analysis of three SNPs (rs12228277: T>A, rs12226937: G>A, and rs61761074: T>G) located in the same region of human KRAS. We found that rs12228277 and rs61761074 result in differential binding patterns of lung nuclear proteins to oligonucleotide probes corresponding two alternative alleles; in both cases, the transcription factor NF-Y is involved. G>A substitution (rs12226937) had no effect on the binding of lung nuclear proteins. However, all the nucleotide substitutions under study showed functional effects in a luciferase reporter assay. Among them, rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer (NSCLC). Taken together, the results of our study suggest that a T>G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.
Добавил в систему: Орлов Юрий Львович

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Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS geneстатья Исследовательская статья

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