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The rs2516839 variation of USF1 gene is associated with 4‐year mortality of nonagenarian women: The Vitality 90+ study
Author(s) -
OzsaitSelcuk B.,
KomurcuBayrak E.,
Jylhä M.,
Luukkaala T.,
Perola M.,
Kristiansson K.,
Mon N.,
Hurme M.,
Kähönen M.,
Goebeler S.,
Laaksonen R.,
Hervonen A.,
ErginelUnaltu.,
Karhunen P.J.,
Lehtimäki T.
Publication year - 2019
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12282
Subject(s) - genotype , hazard ratio , biology , demography , confidence interval , medicine , proportional hazards model , longevity , allele , population , genetics , oncology , gene , sociology
Upstream transcription factor 1 ( USF1 ) regulates the transcription of many genes related to cell and organism survival processes such as stress and immune response, regulation of cellular senesce, and carcinogenesis. In this study, our aim was to investigate the effect of USF1 single nucleotide variations (SNVs) on longevity in the Vitality 90+ study, a population‐based study of nonagenarians (90 ±1 years of age) living in the area of Tampere municipality, Finland. Altogether 509 voluntary nonagenarians (115 males, 394 females) were genotyped using the 5′‐nuclease assay for rs2774279 G > A, rs2516839 T > C, and rs2073658 C > T SNVs. During the 4 years of follow‐up, the total mortality rate was 64.2%. In the study, we found that the frequency of C‐allele of rs2516839 among nonsurviving nonagenarians (52.5%) was higher than those who survived (41.2%; P = 0.0006, odds ratio = 1.575, 95% confidence interval [CI]: 1.215–2.041). Furthermore, carriage of this variation and its haplotypes had a significant gender by genotype interaction ( P < 0.05) on mortality. Kaplan‐Meier log‐rank test during 4‐years of follow‐up showed significantly higher mortality rate in the case of CC genotype carriage than other genotype carriages in nonagenarian women ( P < 0.0001). In addition, after adjusting for age in Cox regression analysis, cardiovascular disease, diabetes, infectious disease, dementia, and living place (nursing home or home), CC genotype of rs2516839 T > C was found to be associated with shorter life expectancy in nonagenarian women (hazard ratio = 2.27; 95% CI, 1.34–3.85 P = 0.002). In conclusion, rs2516839 variation and related haplotypes of the USF1 gene are strongly related to all‐cause mortality in Finnish nonagenarians, especially among women.