TY  - JOUR
AU  - Životić, Ivan
AU  - Đurić, Tamara
AU  - Stanković, Aleksandra
AU  - Milašinović, Dejan
AU  - Stanković, Goran
AU  - Dekleva, Milica
AU  - Marković-Nikolić, Nataša
AU  - Alavantić, Dragan
AU  - Živković, Maja
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8432
AB  - Background: Chromosomal region 9p21.3 is most robustly associated with coronary artery disease (CAD) in western European populations. However, heterogeneity in CAD phenotypes leads to uncertainty whether 9p21.3 is associated with stable and/or acute clinical presentations of CAD. 9p21.3 is rich in regulatory elements, but the underlying mechanisms of its actions in CAD remain unclear. We investigate the association of 9p21.3 two haplotype blocks lead variants (rs10757278 and rs518394) with first-ever non-fatal myocardial infarction (MI) in CAD patients and their association with CDKN2B mRNA expression in peripheral blood mononuclear cells 6 months after the event. Methods: We included CAD patients with sustained first MI (n = 523) and controls (n = 583). Gene expression was assessed in 72 patients 6 months after MI and 43 healthy controls. TaqMan® technology was used for the gene expression and genotyping analysis. Results: CDKN2B mRNA was significantly lower in MI patients compared with the controls (p = 0.002) and in patients carrying the rs10757278 G risk allele versus AA homozygotes (p = 0.012) 6 months after the event. While we confirmed the association of rs10757278 with CDKN2B expression in MI patients, we failed to find an association between the investigated variants and MI or disease burden. Conclusions: We suggest a dysregulation of gene expression in the 9p21.3 region six months after acute MI, which is affected by a genetic variant in patients. The rs10757278 rare allele is one factor that might lead to prolonged risk for proatherogenic complications. © 2019 The Canadian Society of Clinical Chemists
T2  - Clinical Biochemistry
T1  - CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI
VL  - 73
SP  - 70
EP  - 76
DO  - 10.1016/j.clinbiochem.2019.08.003
ER  - 

@article{
author = "Životić, Ivan and Đurić, Tamara and Stanković, Aleksandra and Milašinović, Dejan and Stanković, Goran and Dekleva, Milica and Marković-Nikolić, Nataša and Alavantić, Dragan and Živković, Maja",
year = "2019",
abstract = "Background: Chromosomal region 9p21.3 is most robustly associated with coronary artery disease (CAD) in western European populations. However, heterogeneity in CAD phenotypes leads to uncertainty whether 9p21.3 is associated with stable and/or acute clinical presentations of CAD. 9p21.3 is rich in regulatory elements, but the underlying mechanisms of its actions in CAD remain unclear. We investigate the association of 9p21.3 two haplotype blocks lead variants (rs10757278 and rs518394) with first-ever non-fatal myocardial infarction (MI) in CAD patients and their association with CDKN2B mRNA expression in peripheral blood mononuclear cells 6 months after the event. Methods: We included CAD patients with sustained first MI (n = 523) and controls (n = 583). Gene expression was assessed in 72 patients 6 months after MI and 43 healthy controls. TaqMan® technology was used for the gene expression and genotyping analysis. Results: CDKN2B mRNA was significantly lower in MI patients compared with the controls (p = 0.002) and in patients carrying the rs10757278 G risk allele versus AA homozygotes (p = 0.012) 6 months after the event. While we confirmed the association of rs10757278 with CDKN2B expression in MI patients, we failed to find an association between the investigated variants and MI or disease burden. Conclusions: We suggest a dysregulation of gene expression in the 9p21.3 region six months after acute MI, which is affected by a genetic variant in patients. The rs10757278 rare allele is one factor that might lead to prolonged risk for proatherogenic complications. © 2019 The Canadian Society of Clinical Chemists",
journal = "Clinical Biochemistry",
title = "CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI",
volume = "73",
pages = "70-76",
doi = "10.1016/j.clinbiochem.2019.08.003"
}

Životić, I., Đurić, T., Stanković, A., Milašinović, D., Stanković, G., Dekleva, M., Marković-Nikolić, N., Alavantić, D.,& Živković, M.. (2019). CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI. in Clinical Biochemistry, 73, 70-76.
https://doi.org/10.1016/j.clinbiochem.2019.08.003

Životić I, Đurić T, Stanković A, Milašinović D, Stanković G, Dekleva M, Marković-Nikolić N, Alavantić D, Živković M. CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI. in Clinical Biochemistry. 2019;73:70-76.
doi:10.1016/j.clinbiochem.2019.08.003 .

Životić, Ivan, Đurić, Tamara, Stanković, Aleksandra, Milašinović, Dejan, Stanković, Goran, Dekleva, Milica, Marković-Nikolić, Nataša, Alavantić, Dragan, Živković, Maja, "CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI" in Clinical Biochemistry, 73 (2019):70-76,
https://doi.org/10.1016/j.clinbiochem.2019.08.003 . .

TY  - JOUR
AU  - Životić, Ivan
AU  - Đurić, Tamara
AU  - Stanković, Aleksandra
AU  - Ivancevic, Ilija
AU  - Končar, Igor
AU  - Milašinović, Dejan
AU  - Stanković, Goran
AU  - Alavantić, Dragan
AU  - Živković, Maja
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1843
AB  - The 9p21.3 region is rich in regulatory elements and the variants in this region had been robustly associated with carotid plaque (CP) and coronary artery disease (CAD). Recently, the HACD4 was detected as one of the six 9p21.3 differentially expressed genes associated with accelerated atherosclerosis and greater mean lesion area in the Athsq1 congenic mice. We aimed to investigate association of two potentially regulatory HACD4 variants (rs36212560 I/D, rs2275888 T/C) and their haplotypes with CP occurrence and the level of HACD4 and FOCAD mRNA in human CP tissue. Association study was replicated in CAD patients who suffered the first myocardial infarction. Study included 477 CP patients, 303 healthy controls and replication sample of 224 CAD males from the population of Serbia. Genotypes were determined by polymerase chain reaction (PCR) and real-time PCR using TaqMan (R) technology. The gene expression was detected with TaqMan (R) technology. We have found significant and independent association of DT haplotype with CP presence in men (adjusted OR = 1.64 CI = 1.12-2.42, p = 0.011). The result was replicated in CAD males (adjusted OR = 1.84 CI = 1.21-2.80, p = 0.004). We have found significant effect of the HACD4 rs2275888 on FOCAD mRNA level in human CP tissue. Correction for multiple testing was performed. Independent association of HACD4 haplotypes with atherosclerotic phenotypes connotes a further validation and replication in larger cohorts as well as functional studies to enlighten the potential mechanism of its action in pathophysiology of atherosclerosis.
T2  - Gene
T1  - The HACD4 haplotype as a risk factor for atherosclerosis in males
VL  - 641
SP  - 35
EP  - 40
DO  - 10.1016/j.gene.2017.10.030
ER  - 

@article{
author = "Životić, Ivan and Đurić, Tamara and Stanković, Aleksandra and Ivancevic, Ilija and Končar, Igor and Milašinović, Dejan and Stanković, Goran and Alavantić, Dragan and Živković, Maja",
year = "2018",
abstract = "The 9p21.3 region is rich in regulatory elements and the variants in this region had been robustly associated with carotid plaque (CP) and coronary artery disease (CAD). Recently, the HACD4 was detected as one of the six 9p21.3 differentially expressed genes associated with accelerated atherosclerosis and greater mean lesion area in the Athsq1 congenic mice. We aimed to investigate association of two potentially regulatory HACD4 variants (rs36212560 I/D, rs2275888 T/C) and their haplotypes with CP occurrence and the level of HACD4 and FOCAD mRNA in human CP tissue. Association study was replicated in CAD patients who suffered the first myocardial infarction. Study included 477 CP patients, 303 healthy controls and replication sample of 224 CAD males from the population of Serbia. Genotypes were determined by polymerase chain reaction (PCR) and real-time PCR using TaqMan (R) technology. The gene expression was detected with TaqMan (R) technology. We have found significant and independent association of DT haplotype with CP presence in men (adjusted OR = 1.64 CI = 1.12-2.42, p = 0.011). The result was replicated in CAD males (adjusted OR = 1.84 CI = 1.21-2.80, p = 0.004). We have found significant effect of the HACD4 rs2275888 on FOCAD mRNA level in human CP tissue. Correction for multiple testing was performed. Independent association of HACD4 haplotypes with atherosclerotic phenotypes connotes a further validation and replication in larger cohorts as well as functional studies to enlighten the potential mechanism of its action in pathophysiology of atherosclerosis.",
journal = "Gene",
title = "The HACD4 haplotype as a risk factor for atherosclerosis in males",
volume = "641",
pages = "35-40",
doi = "10.1016/j.gene.2017.10.030"
}

Životić, I., Đurić, T., Stanković, A., Ivancevic, I., Končar, I., Milašinović, D., Stanković, G., Alavantić, D.,& Živković, M.. (2018). The HACD4 haplotype as a risk factor for atherosclerosis in males. in Gene, 641, 35-40.
https://doi.org/10.1016/j.gene.2017.10.030

Životić I, Đurić T, Stanković A, Ivancevic I, Končar I, Milašinović D, Stanković G, Alavantić D, Živković M. The HACD4 haplotype as a risk factor for atherosclerosis in males. in Gene. 2018;641:35-40.
doi:10.1016/j.gene.2017.10.030 .

Životić, Ivan, Đurić, Tamara, Stanković, Aleksandra, Ivancevic, Ilija, Končar, Igor, Milašinović, Dejan, Stanković, Goran, Alavantić, Dragan, Živković, Maja, "The HACD4 haplotype as a risk factor for atherosclerosis in males" in Gene, 641 (2018):35-40,
https://doi.org/10.1016/j.gene.2017.10.030 . .

TY  - CONF
AU  - Životić, Ivan
AU  - Đurić, Tamara
AU  - Stanković, Aleksandra
AU  - Stanković, Goran
AU  - Milašinović, Dejan
AU  - Dekleva, Milica
AU  - Marković-Nikolić, Nataša
AU  - Alavantić, Dragan
AU  - Živković, Maja
PY  - 2018
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0021915018309699
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7953
AB  - Aim: Myocardial infarction (MI) incidence is still a major burden in the
terms of premature death and disability world-wide. Genetic studies up to
date explained a limited portion of disease inheritance. Recently, the DT
haplotype of variants rs36212560 I/D (insertion/deletion) and 2275888 T/C
in HACD gene (9p21.3) have been significantly associated with the risk of
carotid plaque occurrence among males.
Methods: We aimed to validate these results by investigating 518 MI patients (366 males) and 303 (167 males) healthy controls from Serbia. Also, he HACD4 gene expression analysis has been conducted in the peripheral
blood mononuclear cells of 72 MI patients, 6 months after the MI. Results
were obtained using ABI-Prism 7500 RT-PCR for rs2275888 allelic
discrimination and HACD4 mRNA relative quantitation. PCR and acrylamide gel electrophoresis were used to distinguish 5 base pairs
rs36212560 insertion deletion polymorphisms.
Results: Haplotype analysis (using Thesias software) showed that DT
haplotype carriers had significantly higher risk for MI (OR ¼ 1.42, CI 1.08-
1.85, p¼0.01) compared with most frequent IT haplotype. In gender
separated groups association remained significant only among males (OR
¼ 1.76, 1.266-2.46, p¼0.0008). Results were adjusted for MI traditional risk
factors (Age, BMI, HDLC, LDLC, Tg, hypertension and smoking). Investigated
genetic variants were not associated with HACD4 expression. Significant
correlation was found between HACD4 mRNA level and age (r¼0.36,
p¼0.001).
Conclusions: We have shown that rs36212560 and rs2275888 DT haplotype from HACD4 gene is significantly and independently associated with
the MI occurrence in males. Additional studies are needed to confirm these
results.
C3  - Atherosclerosis
T1  - HACD4 haplotype confers risk of myocardial infarction among males in the population of Serbia
VL  - 275
SP  - e210
EP  - e211
DO  - 10.1016/j.atherosclerosis.2018.06.657
ER  - 

@conference{
author = "Životić, Ivan and Đurić, Tamara and Stanković, Aleksandra and Stanković, Goran and Milašinović, Dejan and Dekleva, Milica and Marković-Nikolić, Nataša and Alavantić, Dragan and Živković, Maja",
year = "2018",
abstract = "Aim: Myocardial infarction (MI) incidence is still a major burden in the
terms of premature death and disability world-wide. Genetic studies up to
date explained a limited portion of disease inheritance. Recently, the DT
haplotype of variants rs36212560 I/D (insertion/deletion) and 2275888 T/C
in HACD gene (9p21.3) have been significantly associated with the risk of
carotid plaque occurrence among males.
Methods: We aimed to validate these results by investigating 518 MI patients (366 males) and 303 (167 males) healthy controls from Serbia. Also, he HACD4 gene expression analysis has been conducted in the peripheral
blood mononuclear cells of 72 MI patients, 6 months after the MI. Results
were obtained using ABI-Prism 7500 RT-PCR for rs2275888 allelic
discrimination and HACD4 mRNA relative quantitation. PCR and acrylamide gel electrophoresis were used to distinguish 5 base pairs
rs36212560 insertion deletion polymorphisms.
Results: Haplotype analysis (using Thesias software) showed that DT
haplotype carriers had significantly higher risk for MI (OR ¼ 1.42, CI 1.08-
1.85, p¼0.01) compared with most frequent IT haplotype. In gender
separated groups association remained significant only among males (OR
¼ 1.76, 1.266-2.46, p¼0.0008). Results were adjusted for MI traditional risk
factors (Age, BMI, HDLC, LDLC, Tg, hypertension and smoking). Investigated
genetic variants were not associated with HACD4 expression. Significant
correlation was found between HACD4 mRNA level and age (r¼0.36,
p¼0.001).
Conclusions: We have shown that rs36212560 and rs2275888 DT haplotype from HACD4 gene is significantly and independently associated with
the MI occurrence in males. Additional studies are needed to confirm these
results.",
journal = "Atherosclerosis",
title = "HACD4 haplotype confers risk of myocardial infarction among males in the population of Serbia",
volume = "275",
pages = "e210-e211",
doi = "10.1016/j.atherosclerosis.2018.06.657"
}

Životić, I., Đurić, T., Stanković, A., Stanković, G., Milašinović, D., Dekleva, M., Marković-Nikolić, N., Alavantić, D.,& Živković, M.. (2018). HACD4 haplotype confers risk of myocardial infarction among males in the population of Serbia. in Atherosclerosis, 275, e210-e211.
https://doi.org/10.1016/j.atherosclerosis.2018.06.657

Životić I, Đurić T, Stanković A, Stanković G, Milašinović D, Dekleva M, Marković-Nikolić N, Alavantić D, Živković M. HACD4 haplotype confers risk of myocardial infarction among males in the population of Serbia. in Atherosclerosis. 2018;275:e210-e211.
doi:10.1016/j.atherosclerosis.2018.06.657 .

Životić, Ivan, Đurić, Tamara, Stanković, Aleksandra, Stanković, Goran, Milašinović, Dejan, Dekleva, Milica, Marković-Nikolić, Nataša, Alavantić, Dragan, Živković, Maja, "HACD4 haplotype confers risk of myocardial infarction among males in the population of Serbia" in Atherosclerosis, 275 (2018):e210-e211,
https://doi.org/10.1016/j.atherosclerosis.2018.06.657 . .