The rs2516839 Polymorphism of the USF1 Gene May Modulate Serum Triglyceride Levels in Response to Cigarette Smoking

Niemiec, Paweł; Nowak, Tomasz; Iwanicki, Tomasz; Górczyńska-Kosiorz, Sylwia; Balcerzyk, Anna; Krauze, Jolanta; Grzeszczak, W; Wiecha, Maria; Zak, Iwona

doi:10.3390/ijms160613203

Cited by 9 publications

(15 citation statements)

References 33 publications

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“…Niemiec et al reported that the USF1 rs2516839 polymorphism modified the triglyceride response to smoking, however, triglyceride differences between the CC, CT and TT genotypes were greater in smokers (2.27 ± 0.26, 1.80 ± 0.09, 1.53 ± 0.10 mmol/L, respectively) in accordance with their higher average triglycerides (1.79 ± 0.07 mmol/L) than in nonsmokers (1.49 ± 0.11, 1.46 ± 0.06, 1.57 ± 0.08, respectively) in accordance with their lower concentrations (1.51 ± 0.05 mmol/L) 59 . Ge et al reported that the difference between the CC homozygotes and carriers of the T-allele of CYBA C242T polymorphism was significant in smokers (0.17 mmol/L, P = 0.01) but not nonsmokers (0.04 mmol/L, P = 0.76), which quantile-dependent expressivity would partially attribute to the smokers higher average triglyceride concentrations (1.33 vs. 1.21 mmol/L) 60 .…”

Section: Smokingsupporting

confidence: 68%

“…Environmental factors that distinguish higher vs. lower triglycerides (e.g., obesity, physical inactivity, smoking, alcohol, high-carbohydrate diets, T2DM) are predicted to produce different genetic estimates under quantile-dependent expressivity. Traditionally, these differences have been attributed to gene-environment interactions, where: 1) the effect of the genotype on the phenotype differs by environment [26][27][28][29][30][31][32][33][34][35][36][37][41][42][43][45][46][47][48][49][50][51][52][53][54][55][58][59][60][61][62][63][65][66][67][74][75][76][77][78][79][80] , or equivalently: 2) the effect of the environment on the phenotype differs by genotype 36,[38][39][40]44,…”

Section: Discussionmentioning

confidence: 99%

“…Czerwinski et al in fact reported that the heritability of plasma triglyceride concentrations was higher in smokers (h 2 = 0.70, average triglycerides 1.68 ± 0.06) than nonsmokers (h 2 = 0.42, average triglycerides 1.58 ± 0.03) 58 . With respect to individual loci, smoking is reported to modify the effects on triglycerides of the upstream stimulatory factor 1 (USF1) gene polymorphism rs2516839 59 , C242T polymorphism of the cytochrome b-245 alpha chain (CYBA) gene 60 , -482 C > T in the insulin-responsive element of APOC3 61 , LPL HindIII 53,62 , and LPL rs263 63 .…”

Section: Smokingmentioning

confidence: 99%

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Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Williams

2020

Sci Rep

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Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations paul t. Williams "Quantile-dependent expressivity" is a dependence of genetic effects on whether the phenotype (e.g., triglycerides) is high or low relative to its distribution in the population. Quantile-specific offspringparent regression slopes (β op) were estimated by quantile regression for 6227 offspring-parent pairs. Quantile-specific heritability (h 2), estimated by 2β op /(1 + r spouse), decreased 0.0047 ± 0.0007 (P = 2.9 × 10 −14) for each one-percent decrement in fasting triglyceride concentrations, i.e., h 2 ± Se were: 0.428 ± 0.059, 0.230 ± 0.030, 0.111 ± 0.015, 0.050 ± 0.016, and 0.033 ± 0.010 at the 90th, 75th, 50th, 25th, and 10th percentiles of the triglyceride distribution, respectively. Consistent with quantile-dependent expressivity, 11 drug studies report smaller genotype differences at lower (posttreatment) than higher (pre-treatment) triglyceride concentrations. This meant genotype-specific triglyceride changes could not move in parallel when triglycerides were decreased pharmacologically, so that subtracting pre-treatment from post-treatment triglyceride levels necessarily created a greater triglyceride decrease for the genotype with a higher pre-treatment value (purported precision-medicine genetic markers). In addition, sixty-five purported gene-environment interactions were found to be potentially attributable to triglyceride's quantile-dependent expressivity, including gene-adiposity

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Section: Smokingsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Smokingmentioning

confidence: 99%

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Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Williams

2020

Sci Rep

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“…Natomiast w populacji polskiej Niemiec i wsp. [29] dowiedli, że genotypy USF1 mogą modyfikować stężenie triacylogliceroli i ryzyko rozwoju choroby wieńcowej w odpowiedzi na palenie tytoniu. Analizując genetyczne i środowiskowe czynniki ryzyka, ujawniono, że nosicielstwo allelu C polimorfizmu rs2516839 zwiększa ryzyko choroby wieńcowej u osób palących tytoń względem homozygot TT (model multiplikatywny; SIM = 2,69; 95% CI: 1,21-6,01; p = 0,015).…”

Section: Usf1 W Patologii Wybranych Jednostek Chorobowychunclassified

“…Analizując genetyczne i środowiskowe czynniki ryzyka, ujawniono, że nosicielstwo allelu C polimorfizmu rs2516839 zwiększa ryzyko choroby wieńcowej u osób palących tytoń względem homozygot TT (model multiplikatywny; SIM = 2,69; 95% CI: 1,21-6,01; p = 0,015). Wykazano także związek pomiędzy paleniem tytoniu a wzrostem stężenia TG dodatnio zależny od liczby kopii allelu C [29]. Ponadto ujawniono, że genotyp CC jest związany z ponadnormatywnym stężeniem TG (OR = 1,81; 95% CI: 1,16-2,82; p = 0,008) w odróżnieniu do genotypu TT związanego z obniżonym stężeniem TG (OR = 0,58; 95% CI: 0,32-0,86; p = 0,007).…”

Section: Usf1 W Patologii Wybranych Jednostek Chorobowychunclassified

USF1 w patologii wybranych jednostek chorobowych

Iwanicka

Zak

2017

Pomeranian J Life Sci

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USF1 belongs to a family of transcription factors characterized by highly conserved helix-loop-helix and leucine zipper domains. The USF1 polypeptide is encoded by the USF1 gene located in the long arm of chromosome 1. The USF1 protein can form homodimers or heterodimers with the USF2 polypeptide. Being a subunit of the dimeric upstream transcription factor, USF1 plays multiple roles in the transcription regulation of many genes, which includes the E-box motif in the promoter region. The activation of gene transcription depends on the integrity of the b-HLH-LZ dimerized domains of USF with the region of DNA. The expression of the USF1 gene and the binding abilities of the protein transcription factor to the promoter region of a target gene is regulated by phosphorylation and methylation processes. The transcription factor USF1 regulates the expression of numerous genes involved, e.g. in the cell cycle, cellular proliferation, cellular ageing, stress and immune response, carcinogenesis, and lipid and carbohydrate metabolism. Moreover, the genetic variants of USF1 can be associated, e.g. with changed levels of serum lipids, glucose and specific markers of carcinogenesis. Among the studied polymorphisms of USF1 a group of genetic variants can be identified, which are associated with risk factors for cardiovascular events. USF1 is also one of the main factors for coronary artery disease, metabolic syndrome, diabetes type II, and familial combined hyperlipidemia. Keywords: USF1; polymorphism; coronary artery disease; diabetes mellitus type II; cancers. ABSTRAKT USF1 należy do rodziny czynników transkrypcyjnych charakteryzujących się obecnością wysoce konserwatywnych domen: helisa-pętla-helisa oraz zamka leucynowego. USF1 kodowany jest przez gen USF1, którego locus znajduje się na ramieniu dłu-gim chromosomu 1. Białko USF1 może tworzyć homodimery lub heterodimery z polipeptydem USF2. Będąc podjednostką dimerycznego czynnika transkrypcyjnego, USF1 reguluje ekspresję wielu genów cechujących się obecnością motywu E-box w obrę-bie regionu promotorowego. Aktywacja transkrypcji danego genu jest zależna od integralności zdimeryzowanych domen b-HLH-LZ USF z regionem DNA. Procesy fosforylacji i metylacji mogą regulować zarówno ekspresję samego genu USF1, jak i zdolność wiązania się białkowego czynnika transkrypcyjnego z regionem promotora genu docelowego. Czynnik transkrypcyjny USF1 reguluje ekspresję istotnych genów zaangażowanych m.in. w cykl komórkowy, proliferację komórkową, procesy starzenia komórkowego, reakcję na stres, odpowiedź immunologiczną organizmu, procesy nowotworzenia oraz w metabolizm węglo-wodanów i lipidów. Ponadto warianty polimorficzne genu USF1 mogą być związane m.in. z ponadnormatywnymi stężeniami wskaźników gospodarki lipidowej, glukozy, a także markerów specyficznych dla procesów kancerogenezy. Spośród zbadanych polimorfizmów genu USF1 można wyróżnić grupę wariantów genetycznych, którym przypisuje się również związek z czynnikami ryzyka predysponującymi do wystąpienia zdarzeń sercowo-naczyniow...

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The rs2516839 variation of USF1 gene is associated with 4‐year mortality of nonagenarian women: The Vitality 90+ study

Ozsait-Selcuk

Kömürcü-Bayrak

Jylhä

et al. 2018

Annals of Human Genetics

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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 rs2774279G > A, rs2516839T > C, and rs2073658C > 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 rs2516839T > 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.

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The rs2516839 Polymorphism of the USF1 Gene May Modulate Serum Triglyceride Levels in Response to Cigarette Smoking

Cited by 9 publications

References 33 publications

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

USF1 w patologii wybranych jednostek chorobowych

The rs2516839 variation of USF1 gene is associated with 4‐year mortality of nonagenarian women: The Vitality 90+ study

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