Influence of Chromosome 9p21.3 rs1333049 Variant on Telomere Length and Their Interactive Impact on the Prognosis of Coronary Artery Disease.

BACKGROUND: Both telomere shortening and the chromosome 9p21.3 (Chr9p21) rs1333049 (G/C) variant are involved in coronary artery disease (CAD) risk, likely affecting mechanisms related to cell cycle arrest and vascular senescence. The aim of the study was to examine the link between Chr9p21 rs1333049 variant and leucocyte telomere length (LTL), as well as their interactive effect on the risk of major adverse cardiovascular events (MACEs). METHODS: A cohort of 472 patients with angiographically proven and clinically stable CAD were included in the study. At baseline, the LTL, biochemical parameters, and genotype analysis of Chr9p21 rs1333049 variant were measured in all patients. The primary endpoint of this study was the occurrence of MACE defined as a composite of coronary-related death, nonfatal MI, and coronary revascularization. RESULTS: On multivariable linear regression analysis, age (p = 0.02) and Chr9p21 rs1333049 variant (p = 0.002) were the only independent predictors of LTL levels. Carriers of the CC genotype of this SNP had shorter telomeres than GC carriers (p = 0.02) and GG carriers (p = 0.0005). After a follow-up with a mean period of 62 ± 19 months, 90 patients (19.1%) had MACE. Short LTL was an independent prognostic factor of MACE incidence (HR:2.2; 95% CI: 1.3-3.7; p = 0.005) after adjustment for potential confounders. There was a significant interaction (p = 0.01) between the LTL and rs1333049 variant, with patients with risk-allele C and short LTL having a higher risk (HR:5.8; 95% CI: 1.8-19.2; p = 0.004). CONCLUSION: A strong relationship between LTL and Chr9p21 rs1333049 variant was identified, and they interactively affect the risk of poor prognosis in CAD patients.

Association of Common Variants of APOE, CETP, and the 9p21.3 Chromosomal Region with the Risk of Myocardial Infarction: A Prospective Study.

The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. This study was aimed at analyzing possible associations of several genetic factors with the risk of myocardial infarction (MI). For our study, we selected genes that have been significantly associated with MI in meta-analyses: the chromosomal region 9p21.3, the CETP gene, and the APOE gene. In total, 2286 randomly selected patients were included. Rs708272 and rs429358 and rs7412 were analyzed using RT-PCR via the TaqMan principle, and rs1333049 vas analyzed via a commercial KASP assay. In our sample, the frequencies of alleles and genotypes were consistent with frequencies in comparable populations of Eastern and Western Europe. Allele C of rs1333049 was significantly associated with MI among males (p = 0.027) and in the whole study sample (p = 0.008). We also revealed a significant association of the ɛ2/ɛ4 genotype of APOE with MI among males (p < 0.0001) and in the whole study sample (p < 0.0001). Thus, among the tested polymorphisms, some genotypes of rs1333049 and rs429358 and rs7412 are the most strongly associated with MI and can be recommended for inclusion into a genetic risk score.

Association of Myocardial Infarction with CDKN2B Antisense RNA 1 (CDKN2B-AS1) rs1333049 Polymorphism in Slovenian Subjects with Type 2 Diabetes Mellitus.

BACKGROUND: We examined the role of rs1333049 polymorphism of the CDKN2B Antisense RNA 1 (CDKN2B-AS1) on the prevalence of myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). METHODS: A total of 1071 subjects with T2DM were enrolled in this retrospective cross-sectional case-control study. Of the subjects, 334 had a history of recent MI, and 737 subjects in the control group had no clinical signs of coronary artery disease (CAD). With logistic regression, we performed a genetic analysis of rs1333049 polymorphism in all subjects. RESULTS: The C allele of rs1333049 polymorphism was statistically more frequent in MI subjects (p = 0.05). Subjects with CC genotype had a higher prevalence of MI than the control group in the co-dominant (AOR 1.50, CI 1.02-2.21, p = 0.04) and recessive (AOR 1.38, CI 1.09-1.89, p = 0.04) genetic model. CONCLUSIONS: According to our study, the C allele and CC genotype of rs1333049 polymorphism of CDKN2B-AS1 are possible markers of MI in T2DM subjects in the Slovenian population.

Association between Coronary Artery Disease and rs10757278 and rs1333049 Polymorphisms in 9p21 Locus in Iran.

BACKGROUND: Coronary arteries disease (CAD) has been recognized as one of the most common causes of death worldwide, with an estimated seven million deaths annually. METHODS: Two hundred blood samples from Iranian CAD patients and normal healthy controls were collected. CAD and the 9p21 locus variants rs1333049 and rs10757278 were analyzed for potential associations. RESULTS: No significant differences in rs10757278 and rs1333049 polymorphisms were found between patients and controls, but a significant relationship was found between rs10757278 and rs1333049 in CAD patients at the genotype level (p= 0.0323). At the haplotype level and on the basis of diplotype analysis, a significant relationship was found between patients and controls (OR= 5.16, p= 0.047, 95% CI: 1.02-26.0). In CAD patients, rs10757278 and rs1333049 were associated at locus 9p21. CONCLUSION: The inconsistency between the results of this and other studies on different CAD populations may be due to high population, different ethnicities, low prevalence of some alleles in populations, and interactions of different genes.

Association of cyclin-dependent kinase inhibitor 2A/B with increased risk of developing breast cancer.

There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real-time polymerase chain reaction (RT-PCR) method and gene expression analysis was ran by RT-PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4-5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.

Analysis of Polymorphism rs1333049 (Located at 9P21.3) in the White Population of Western Siberia and Associations with Clinical and Biochemical Markers.

The 9p21.3 chromosomal region is a marker of the risk of cardiovascular diseases. The aim of this study was to analyze single-nucleotide polymorphism rs1333049 (chr9:22125504) in the population of Western Siberia (Russia) and possible associations with clinical and biochemical parameters. The population included in the analyses was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 participants, >90% white, aged 45-69, males: 50%). In total, 2729 randomly selected patients were included. Plasma lipid levels were determined by standard enzymatic assays. Rs1333049 was analyzed by RT-PCR (BioLabMix, Russia). Frequencies of rs1333049 genotypes C/C (homozygote), C/G (heterozygote), and G/G were 0.22, 0.51, and 0.27 in this population. The Allele G frequency was 0.53. We found an association of allele G with total cholesterol and low-density lipoprotein cholesterol levels among male participants (p = 0.004 and p = 0.002, respectively). Allele C was significantly associated with the risk of myocardial infarction among the male participants (odds ratio 1.96, 95% confidence interval 1.14-3.38, p = 0.017) and the study population (odds ratio 1.83, 95% confidence interval 1.23-2.72, p = 0.004). Thus, rs1333049 is associated with myocardial infarction in the white population of Western Siberia (Russia).

Association study of two single nucleotide polymorphisms rs10757278 and rs1333049 with atherosclerosis, a case-control study from Iraq.

Atherosclerosis is one of the most important coronary artery disease (CAD) caused by lipid accumulation, hypertension, smoking, and many other factors such as environmental and genetic factors. It has been recorded that genetic variations in rs10757278 and rs1333049 are correlated with CAD. In the present study, 100 blood samples were collected (50 CAD patients and 50 appeared to be healthy controls), who referred to Ibn-Albytar general hospital/in Bagdad city for heart disease from February to March 2019. Genotyping for two SNPs rs10757278 and rs1333049, were done by Tetra ARMS method. For the rs10757278 polymorphism, the GG genotype verses to AA genotype was significantly associated with the risk of CAD (OR=5.16, 95% CI:1.02-26.0, P=0.047). For the rs10757278 polymorphism, there was no significant associatin between genotypes and the susceptibiulity to CAD. In the present study, the rs10757278 polymorphism showed an association with CAD.

Association of the single nucleotide polymorphism in chromosome 9p21 and chromosome 9q33 with coronary artery disease in Chinese population.

BACKGROUND: Our study aims to explore the association of rs7025486 single-nucleotide polymorphisms (SNP) in DAB2IP and rs1333049 on chromosome 9p21.3 with the coronary artery disease in Chinese population. METHODS: All patients came from the east China area and underwent coronary angiography. Rs7025486 and rs1333049 polymorphism were genotyped in 555 patients with CAD and in 480 healthy controls that underwent coronary angiography. RESULTS: In Chinese population, the rs7025486 genotype in the case group was no significant different than the control group (P = 0.531).Meanwhile, the rs1333049 SNP has statistically significant (P = 0.006), which was the independent risk factors for CAD (OR1.252, P = 0.039), and consistent with the past studies conclusion. CONCLUSION: Genotype of rs1333049 on chromosome 9p21, but not rs7025486 on chromosome 9q33, is an independent determinant of the incidence of CAD in Chinese population.

Association of CDKN2B-AS1 rs1333049 with Brain Diseases: A Case-control Study and a Meta-analysis.

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p＜0.001) and total cholesterol (TC) (p＜0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p＞0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08-1.25; p＜0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.

Association of CDKN2B-AS1 rs1333049 with Brain Diseases: A Case-control Study and a Meta-analysis

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08–1.25; p<0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.