Dataset Information

Association between Serum Kalirin Levels and the KALRN gene rs9289231 Polymorphism in Early-Onset Coronary Artery Disease.

ABSTRACT: Background: Recently, rs9289231 genetic variations of kalirin (KALRN) have been introduced as potential genetic markers for coronary artery disease (CAD). However, the influence of KALRN single-nucleotide polymorphisms (SNPs) on serum kalirin levels has not been investigated in CAD patients so far. Thus, the present study aimed to survey whether SNP T>G (rs9289231) was associated with the risk of early-onset CAD and serum kalirin levels among the study subjects. Methods: The rs9289231 polymorphism of the KALRN was genotyped in 512 subjects (61.5% male, mean age=46.3±7.1 y), comprising 268 subjects with angiographically diagnosed CAD and 244 controls using an HRM assay. Also, the levels of serum kalirin were compared between 133 CAD subjects and 123 controls using a sandwich ELISA assay. Results: The CAD subjects had more frequently GG genotypes than the controls. The odds ratio (OR) remained significant after adjustment for known CAD risk factors (OR=4.13, 95% CI: 2.48-9.10; P<0.001). A significant difference was also observed in that the G allele was more frequent among the CAD subjects. The G allele at the rs9289231 polymorphism was associated with a higher risk of CAD (OR=2.11, 95% CI: 1.27-2.59; P=0.001). The mean kalirin level of the CAD patients was higher than that of the controls (P=0.041). No significant correlation was seen in the different genotypes with serum kalirin levels. Conclusion: The KALRN rs9289231 T>G variant was considerably related with an increased risk of early-onset CAD. High kalirin levels were found in young CAD patients compared to the control subjects, with the levels not affected by the different genotypes of rs9289231.

SUBMITTER: Shafiei A

PROVIDER: S-EPMC6246431 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Association between Serum Kalirin Levels and the KALRN gene rs9289231 Polymorphism in Early-Onset Coronary Artery Disease.

Shafiei Afsaneh A Pilehvar-Soltanahmadi Younes Y Ziaee Shayan S Mofarrah Mohsen M Zarghami Nosratollah N

The journal of Tehran Heart Center 20180401 2

Background: Recently, rs9289231 genetic variations of kalirin (KALRN) have been introduced as potential genetic markers for coronary artery disease (CAD). However, the influence of KALRN single-nucleotide polymorphisms (SNPs) on serum kalirin levels has not been investigated in CAD patients so far. Thus, the present study aimed to survey whether SNP T>G (rs9289231) was associated with the risk of early-onset CAD and serum kalirin levels among the study subjects. Methods: The rs9289 ...[more]

PMID: 30483314

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Project description:BackgroundThe relationship between galectin-3 (Gal-3) and coronary artery disease (CAD) has not been fully elucidated.AimThis study aimed to determine the relationship between the presence and severity of CAD and serum Gal-3 levels.Patients and methodsThree-hundred thirty-one consecutive CAD patients were enrolled as the study group. An additional 62 patients without CAD were enrolled as the control group. Serum Gal-3 levels were separately compared between the non-CAD and CAD groups, among the stable CAD and Acute coronary syndrome (ACS) groups, and between CAD patients with low and high SYNTAX scores (SSs). The 1-year cumulative rate of major adverse cardiac events (MACEs) was also compared among ACS patients by Gal-3 levels.ResultsSerum Gal-3 was significantly higher in the CAD group than in the non-CAD group 3.89 (0.16-63.67) vs. 2.07 (0.23-9.38) ng/ml, P < 0.001. Furthermore, serum Gal-3 was significantly higher in the non-ST-segment elevation ACS (NSTE-ACS) group than that in the stable CAD group, 4.72 (1.0-16.14) vs. 2.23 (0.65-23.8) ng/ml, P = 0.04 and higher in the ST-segment elevation myocardial infarction (STEMI) group than that in the stable CAD group 7.87 (0.59-63.67) vs. 2.23 (0.65-23.8) ng/ml, P < 0.001. Serum Gal-3 level was an independent predictor of ACS compared with stable CAD group (OR = 1.131, 95% CI: 1.051-1.217, P = 0.001) as well as high SS (OR = 1.030, 95% CI: 1.021-1.047, P = 0.038) after adjust other confounding risk factors. Acute coronary syndrome patients with Gal-3 levels above the median (gal-3 = 4.78 ng/ml) showed a higher cumulative MACE rate than those with Gal-3 levels below the median. After adjusting other confounding risk factors, Gal-3 remained an independent risk factor for the cumulative rate of MACEs in ACS patients (6% higher rate of MACEs incidence per 1 ng/ml increment of Gal-3).ConclusionGalectin-3 correlated with the presence of CAD as well as coronary stability and complexity. Galectin-3 may be valuable in predicting mid-term prognosis in ACS patients.

Project description:Importance:Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction. Objective:To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization. Design, Setting, and Participants:The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N?=?up to 61?079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N?=?up to 184?305 individuals) that included cases (individuals with CAD and myocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD and myocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis. Exposures:Genetic risk score based on genetic variants related to elevated serum calcium levels. Main Outcomes and Measures:Co-primary outcomes were the odds of CAD and myocardial infarction. Results:Among the mendelian randomized analytic sample of 184?305 individuals (60?801 CAD cases [approximately 70% with myocardial infarction] and 123?504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P?=?.003) for CAD and 1.24 (95% CI, 1.05-1.46; P?=?.009) for myocardial infarction. Conclusions and Relevance:A genetic predisposition to higher serum calcium levels was associated with increased risk of CAD and myocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

Project description:Homocysteine (Hcy) elevation and vitamin D deficiency have emerged as potential markers of coronary artery disease (CAD). However, even tough hypovitaminosis D has been suggested to interfere with Hcy catabolism, no study has so far addressed the interaction of vitamin D and Hcy and their impact on CAD, that was the aim of present study. A cohort of consecutive patients undergoing coronary angiography in a single center were included and analyzed within the year 2019. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or three-vessel disease. Hcy and vitamin D levels were assesssed at admission. We included 3150 patients undergoing coronary angiography at our centre, who were divided according to the quartiles values of vitamin D. Patients with lower levels of Vitamin D displayed a higher cardiovascular risk profile and a higher prevalence of CAD. We observed an inverse linear relationship between lower levels of vitamin D and higher Hcy (r = - 0.092, p < 0.001) and a higher prevalence of hyperhomocysteinemia in patients with lower quartiles values of vitamin D (p < 0.001). By forward conditional regression model, low vitamin D appeared as independent predictors of Homocysteine levels above the median (OR[95%CI] = 1.79[1.37-2.33], p < 0.001). In addition, patients with low vitamin D (below the median) and increased Hcy displayed a non-significantly higher rate of CAD (81% vs 77.7%, p = 0.13, adjusted OR[95%CI] = 1.16[0.88-1.54], p = 0.29) but a significant increase in the rate of severe left main/3-vessel CAD (37.4% vs 30.5%, p = 0.005, adjusted OR[95%CI] = 1.29[1.02-1.67], p = 0.04). Among patients with vitamin D levels above the median, Hcy levels did not impact on the prevalence and extent of CAD (77.7 vs 77.2%, p = 0.81, adjusted OR[95%CI] = 0.94[0.73-1.20], p = 0.60 for CAD and 31.8% vs 27.7%, p = 0.08, adjusted OR[95%CI] = 0.97[0.75-1.25], p = 0.81 for severe left main/3-vessel CAD). No significant interaction between Hcy and vitamin D with CAD or severe CAD was observed. The present study shows an independent inverse linear relationship between vitamin D and Hcy values. Moreover, the association of Hcy with the extent of CAD was significant only among patients with hypovitaminosis D, and not in the cohort of subjects with vitamin D levels above the median, suggesting that a normal vitamin D status can prevent the deleterious effects of hyperhomocysteinemia on coronary atherosclerosis, a hypothesis that certainly needs further confirmation in larger randomized trials.

Dataset Information

Association between Serum Kalirin Levels and the KALRN gene rs9289231 Polymorphism in Early-Onset Coronary Artery Disease.

Publications

Association between Serum Kalirin Levels and the <i>KALRN</i> gene rs9289231 Polymorphism in Early-Onset Coronary Artery Disease.

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