9p21 Locus Polymorphisms: Risk and Severity Factors of Coronary Artery Disease in Venezuelan Patients

Abstract Background: The 9p21 region is the most relevant locus associated with coronary heart disease in different populations. However, there are no studies that prove that this region is a risk factor in the Venezuelan population. Objectives: To analyze whether or not the 9p21 rs1333049 polymorphism is a risk factor for acute myocardial infarction (AMI) in Venezuelan patients, as well as to investigate its correlation with cardiovascular risk factors (CVRF), age of occurrence, type and severity of infarction, and the correlation of the rs10757274 polymorphism with severity of coronary artery disease. Methods: This was an association study, including 487 unrelated Venezuelan individuals, grouped in 354 patients with AMI and 133 controls. The rs1333049 and rs10757274 polymorphisms were determined using the polymerase chain reaction (PCR) technique with sequence-specific primers. The analysis of association was determined using the SNPStats tool. The continuous variable description and the correlations were performed using the SPSS statistical software. Significance was established at p<0.05. Results: A positive correlation was observed between the rs1333049 polymorphism and the presence of hypertension ( r: 0.145, p: 0.006), and between hypertension and heart infarction ( r: 0.318, p: <0.0001). A positive correlation was found between the rs10757274 polymorphism and the number of coronary vessels that presented obstructive lesions in patients aged ≤ 55 years ( r: 0.276, p: 0.0078). Conclusion: The rs1333049 polymorphism at the 9p21 locus is correlated with hypertension in Venezuelan patients, while the rs10757274 polymorphism is associated with the progression of coronary atherosclerosis, suggested by the correlation with the number of coronary vessels that presented significant obstructive lesions.

Genetic variants of chromosome 9p21.3 region associated with coronary artery disease and premature coronary artery disease in an Asian Indian population

Introduction Asian Indians have a propensity for premature, severe, and diffuse coronary artery disease (CAD). Several single-nucleotide polymorphisms (SNPs) in the ‘core CAD’ region of the chromosomal region 9p21.3 are known to be strongly associated with CAD. Objectives We aimed to study SNPs in the 9p21.3 region associated with CAD and premature CAD and identify their association with demographic and clinical characteristics in an Asian Indian population. Methods SNP genotyping was performed for 30 SNPs of the 9p21.3 region using MassARRAY® technology. Along with demographic and SNP data analysis, we also performed multivariate logistic regression analysis and multifactor dimensionality reduction analysis to study SNP–SNP and SNP–demographic/clinical variable interactions. Results Our results suggest that females are at a higher risk of premature CAD. We found that SNPs rs1333045 (CC), rs16905599 (AA), rs2383206 (GG), rs2383208 (AG), and rs4977574 (GG) were significantly associated with premature CAD. When adjusted for covariates/confounders, we found that rs2383206 showed the strongest risk association with CAD followed by rs16905599 and rs2383208. Further, SNPs rs1333049 (CC) and rs4977574 (GG) were found to be exclusively associated with premature CAD cases, suggesting their potential as genetic markers for premature CAD in the local population. Upon gender-based stratification, it was found that rs10757272 (TT and TC) is significantly associated with eightfold to ninefold CAD risk specifically among females. SNP rs7865618 (GG) is significantly associated with more than 2.5-fold CAD risk specifically among males. Conclusion Our study suggests that SNPs at the 9p21 risk locus may be used to generate a reliable genetic risk score along with markers at other loci.

Association between genetic variations in 9p21 region and coronary heart disease in Chinese Han population / 吉林大学学报(医学版)

Objective: To analyze the association of the genetic variations of rs2383206 and rs2383207 in 9p21 region with the coronary heart disease (CHD) in the Chinese Han population, and to explore whether chromosome 9p21 is a susceptibility region for CHD. Methods: Case-control study was conducted. A total of 580 CHD patients were selected as case group, and 539 cases of non-cardiovascular disease patients or normal people with matched age and sex were selected as control group. The rs2383206 and rs2383207 loci of the subjects were genotyped with Sequenom Mass ARRAY time of flight mass spectrometer (TOF). Results: The smoking, waist-to-hip ratio (WHR), hypertension, diabetes mellitus, systolic blood pressure (SBP), diastolic blood pressure (DBP) and total cholesterol (TC of the subjects in two groups were statistically different (P0. 05), while the genotypic distribution of rs2383207 was statistically different (X2 =8. 936, P<0. 05); the distribution frequency of AA genotype in case group (8. 3%) was significantly lower than that in control group (13.6%) (P<0. 05). Conclusion: Smoking, WHR, hypertension, diabetes mellitus, SBP, DBP and TC may be the risk factors for CHD; the AA genotype of 9p21 rs2383207 loci may be the protective genotype of CHD.

Association between genetic variations in 9p21 region and coronary heart disease in Chinese Han population / 吉林大学学报(医学版)

Objective:To analyze the association of the genetic variations of rs2383206 and rs2383207 in 9p21region with the coronary heart disease (CHD) in the Chinese Han population,and to explore whether chromosome 9p21 is a susceptibility region for CHD.Methods:Case-control study was conducted.A total of 580 CHD patients were selected as case group,and 539 cases of non-cardiovascular disease patients or normal people with matched age and sex were selected as control group.The rs2383206 and rs2383207 loci of the subjects were genotyped with Sequenom MassARRAY time of flight mass spectrometer (TOF).Results:The smoking,waist-to-hip ratio (WHR),hypertension,diabetes mellitus,systolic blood pressure (SBP),diastolic blood pressure (DBP) and total cholesterol (TC) of the subjects in two groups were statistically different (P＜0.05).Compared with control group,the ratios of patients with smoking,hypertension and diabetes mellitus of the patients in case group were increased (P＜0.05);the WHR,SBP,DBP and TC level were also increased (P＜0.05).There was no significant difference in the genotypic distribution of rs2383206 between case group and control group (x2 =4.623,P＞0.05),while the genotypic distribution of rs2383207 was statistically different (x2 =8.936,P＜0.05);the distribution frequency of AA genotype in case group (8.3％) was significantly lower than that in control group (13.6％) (P＜0.05).Conclusion:Smoking,WHR,hypertension,diabetes mellitus,SBP,DBP and TC may be the risk factors for CHD;the AA genotype of 9p21 rs2383207 loci may be the protective genotype of CHD.

The Association of SNP on Chromosome 9p21 with Myocardial Infarction in Yunnan Yi nationality / 中国生化药物杂志

Objective To investigate the relationship between 9p21 single nucleotide polymorphism (SNP) and myocardial infarction(MI) in Yunnan Yi nationality. Methods One hundred and ten patients with MI and 110 controls were enrolled. DNA sequencing was used to detect 9p21 gene locus and SNP typing and analysis. Results Hardy-Weinberg equilibrium was found in 9 sites of chromosome 9p21 in myocardial infarction group and control group.The frequency of rs1333049 GG genotype was 30.91% and 18.18% in case group and control group respectively, G The frequencies of rs2383206 GG genotype were 31.82% and 18.18%, respectively, and the frequencies of G allele were 55.3% and 41.1%, respectively. There were significant differences between the two groups 58.3% and 44.9%, The difference between the two groups was statistically significant(P<0.05). Conclusion This study demonstrates an association of rs1333049 polymorphism locus on chromosome 9p21 with risk for MI in in Yunnan Yi nationality.

Association between chromosome 9p21 polymorphism and the large-artery atherosclerosis stroke / 中国神经精神疾病杂志

Objective To explore the association between rs7049105, rs647188, rs1333035 of chromosome 9p21 and the LAS among Chinese Han population of Changsha;to explore the association between rs7049105, rs647188, rs1333035 and the LAS among patients with evidence of cephalic and cervical vessel atherosclerosis. Methods The present study com?prised 229 LAS patients and 233 healthy controls. The 233 controls which we defined control group 1. In the controls, 150 (64.38%)controls with evidence of atherosclerosis were defined as control group 2, 83(35.62%)controls without evidence of atherosclerosis were defined as control group 3. The sample genotyping was detected using MALDI-TOF-MS. Results There was no polymorphism of rs647188 among case group and control group 1. There was no significant difference in the polymorphism distribution of rs7049105 and rs1333035 between the case group and control group 1 and 3 (P>0.05). There may be no significant different in the polymorphism distribution of rs7049105 between the case group and control group 2 . The rs1333035 was associated with risk of LAS among patients with evidence of cephalic and cervical vessel atherosclerosis (χ2=6.502,P=0.039). Conclusions The rs10757274 and rs7049105 polymorphism in the chromosome 9p21 may not be as?sociated with risk of LAS among Han population of Changsha. There may be no polymorphism of rs647188 among Han popu?lation of Changsha. The rs1333035 polymorphism may be associated with plaque rupture and thrombosis.

The correlation study between the distribution of two single nucleotide polymorphism(SNP)loci on chromo-some 9p21 and the macrovascular disease in Xinjiang Uygur and Han nationality people with type 2 diabetes / 中国基层医药

Objective To assessed the distribution of two single nucleotide polymorphism (SNP)loci (rs2383206.rs10757278)on chromosome 9p21 in Xinjiang Uygur and Han nationality populations,and to investigate correlation and the incidence of all cases of macrovascular disease (coronary artery disease,carotid atherosclerosis and peripheral arterial disease)and analysis of risk factors.To further study the correlation between the incidence of two single nucleotide polymorphism (SNP)loci (rs2383206.rs10757278)on chromosome 9p21 in type 2 diabetes melli-tus(T2DM)of Han and Uygur ethnic and the incidence of all cases vascular disease,then to analysis the risk factors. Methods 497 adults with T2DM who were treated in the Endocrinology department in hospital from May 2012 to April 2014 were involved in this study,including 298 Uygur patients and 199 Han patients.215 non -T2DMpatients who were treated in the Cardiology department in hospital were also involved in the study,including 93 Uighur patients and 122 Han patients.Then the total 712 patients were detectedby using PCR -SNP Stream technology to analyse rs2383206.rs10757278 loci SNP genotyping.The relevant results were compared with t test,two different genotype distribution and allele frequency were compared with χ2 test,multiple factors analysis were calculated by Logisitic regression.Results The distribution of genotype with two SNP loci had no significant difference between the patients in Uygur group and Han group (rs2383206χ2 =5.570,P =0.062;rs10757278 χ2 =2.721,P =0.257 ),and there's no significant difference between the patients with macrovascular disease and non -macrovascular disease in all patients(rs2383206χ2 =0.120,P =0.950;rs10757278 χ2 =1.027,P =0.598).Logisitic regression analysis showed that the incidence of macrovascular was significantly associated with increasing age(χ2 =28.820,P =0.000)and fatty liver(χ2 =5.210,P =0.020)in Uighur group with type 2 DM.In Han group with type 2 DM,the macrovascular was significantly associated with the increase of age (χ2 =19.980,P =0.000),elevated fasting blood glucose (FPG)(χ2 =4.070,P =0.044)and poor controlled with glycosylated hemoglobin (χ2 =4.280,P =0.040). Conclusion This study found that there's no correlation between two single nucleotide polymorphisms (SNPS)loci (rs2383206.rs10757278)on chromosome 9 p21 large with macrovascular in Uygur group and Han group.Increasing age,higher FPG and poor controlled with glycosylated hemoglobin combined with fatty liver were the risk factors for macrovascular.

Loss of Heterozygosity on Chromosome 9p21, 17p13 and 3p in Human Astrocytic Tumor

BACKGROUND: The purpose of this study was to determine the genetic abnormalities of chromosomes 9p21, 17p13.1, 3p25 and 3p14.2 in the development and progression of astrocytic tumors. METHODS: We performed loss of heterozygosity (LOH) analysis in 41 astrocytic tumors, including 20 astrocytomas, 11 anaplastic astrocytomas and 10 glioblastomas, and correlated the results of LOH at different histopathologic grades. LOH was determined by multiplex polymerase chain reaction analysis of the DNA, which was extracted by microdissection. RESULTS: LOH of 9p21 was found in 55.6% of astrocytomas, 54.6% of anaplastic astrocytomas and 100.0% of glioblastomas. LOH of 17p13.1 was found in 21.4% of astrocytomas, 28.6% of anaplastic astrocytomas, and 66.7% of glioblastomas. LOH of 3p25 was found in 37.5% of astrocytomas, 16.7% of anaplastic astrocytomas, and 14.3% of glioblastomas. LOH of 3p14.2 was found in 16.7% of astrocytomas, 40.0% of anaplastic astrocytomas, and 42.9% of glioblastomas. LOH on chromosome 9p21 and 17p13.1 was closely related with the histopathologic grades. CONCLUSIONS: These results may suggest that LOH of 9p21, 17p13.1, 3p25 and 3p14.2 involves an early event of astrocytoma development and accumulates during progression. LOH of 3p25 may be involved in the tumorigenesis of astrocytoma. Identification of these LOH may illuminate the stepwise pathogenesis of astrocytic tumors and predict the possibility of malignant transformation.

Deletions of 9p21 and TP53 in bladder cancer

The objective of this study was to characterize the alterations of 9p21 and TP53 in Korean transitional bladder cancer and to assess the relationship between the histopathologic parameter and the alteration of these genes. Allele loss in 29 surgically resected transitional cell carcinoma was examined by using the multiplex PCR with 7 and 1 microsatellite markers for 9p21 and TP53, respectively. Twenty-one (72%) demonstrated allele loss at 9p21 and/or TP53. Deletion at the 9p21 region was detected in 17(61%) of 28 informative cases at one or more loci, and LOH at TP53 was found in 12(55%) of 22 informative cases. Of 7 microsatellite markers for 9p21, allele loss occurred the most frequently at locus D9S162(69%) and D9S104(69%). Additionally, hemizygous deletion was slightly more common than homozygous deletion. Deletion at 9p21 and TP53 was not related with increased grade. These results suggest that the alteration of 9p21 may be an early event in the development of Korean bladder cancer, while p53 gene may be involved in early event of some bladder cancers as well as in their late events.