scholarly journals The rs3737964 single‐nucleotide polymorphism of the chloride channel‐6 gene as a risk factor for coronary heart disease

2015 ◽  
Vol 3 (6) ◽  
pp. 537-542 ◽  
Author(s):  
Li Zhang ◽  
Tao Zhang ◽  
Zhengkai Xiang ◽  
Shengqiang Lu
Keyword(s):  
Coronary Heart Disease ◽  
Single Nucleotide Polymorphism ◽  
Risk Factor ◽  
Heart Disease ◽  
Chloride Channel ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals Assessment of the clinical utility of adding common single nucleotide polymorphism genetic scores to classical risk factor algorithms in coronary heart disease risk prediction in UK men

2017 ◽  
Vol 55 (10) ◽  
Author(s):  
Katherine E. Beaney ◽  
Jackie A. Cooper ◽  
Fotios Drenos ◽  
Steve E. Humphries
Keyword(s):  
Coronary Heart Disease ◽  
Single Nucleotide Polymorphism ◽  
Heart Disease ◽  
Standard Deviation ◽  
Risk Prediction ◽  
Clinical Utility ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

AbstractBackground:Risk prediction algorithms for coronary heart disease (CHD) are recommended for clinical use. However, their predictive ability remains modest and the inclusion of genetic risk may improve their performance.Methods:QRISK2 was used to assess CHD risk using conventional risk factors (CRFs). The performance of a 19 single nucleotide polymorphism (SNP) gene score (GS) for CHD including variants identified by genome-wide association study and candidate gene studies (weighted using the results from the CARDIoGRAMplusC4D meta-analysis) was assessed using the second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases). To improve the GS, five SNPs with weak evidence of an association with CHD were removed and replaced with seven robustly associated SNPs – giving a 21-SNP GS.Results:The weighted 19 SNP GS was associated with lipid traits (p<0.05) and CHD after adjustment for CRFs, (OR=1.31 per standard deviation, p=0.03). Addition of the 19 SNP GS to QRISK2 showed improved discrimination (area under the receiver operator characteristic curve 0.68 vs. 0.70 p=0.02), a positive net reclassification index (0.07, p=0.04) compared to QRISK2 alone and maintained good calibration (p=0.17). The 21-SNP GS was also associated with CHD after adjustment for CRFs (OR=1.39 per standard deviation, 1.42×10Conclusions:The 19-SNP GS is robustly associated with CHD and showed potential clinical utility in the UK population.

Functional association of a CD40 gene single-nucleotide polymorphism with the pathogenesis of coronary heart disease

2019 ◽  
Vol 116 (6) ◽  
pp. 1214-1225 ◽  
Author(s):  
Cheryl S Sultan ◽  
Michael Weitnauer ◽  
Martin Turinsky ◽  
Thorsten Kessler ◽  
Maik Brune ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Single Nucleotide Polymorphism ◽  
Heart Disease ◽  
Asian Population ◽  
Serum Levels ◽  
Cd40 Ligand ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Cd40 Gene ◽  
Ligand Interactions

Abstract Aims Endothelial dysfunction is a major contributor to the pathogenesis of atherosclerosis. CD40–CD40 ligand interactions confer a pro-inflammatory phenotype to endothelial cells (ECs). Recently, a thymine to cytosine transition (−1T&gt;C) in the Kozak sequence of the CD40 gene (rs1883832) has been associated with coronary heart disease (CHD) in an Asian population. As there are no reports yet regarding its role in other ethnic groups, this study determines if the −1T&gt;C single-nucleotide polymorphism (SNP) could be a risk factor for CHD in Caucasians by performing an association study and elucidates its functional consequence in cultured ECs. Methods and results Molecular and biochemical techniques, cell adhesion assays were used for genotype-stratified human EC characterization. SNP distribution in Caucasians was examined in a hospital-based case–control CHD study and serum levels of soluble CD40 (sCD40) were quantified by ELISA. The SNP in the CD40 gene affected baseline CD40 protein abundance on ECs. There was a genotype-dependent difference in CD40-mediated expression of pro-inflammatory genes. Monocyte adhesion was highest on the surface of cells homozygous for the C allele. Homozygosity for the C allele was associated with significant 2.32-fold higher odds of developing CHD as compared to TT genotype carriers. sCD40 plasma levels were genotype-dependently elevated in CHD patients, indicating a possible prognostic value. Conclusion The C allele of the CD40 SNP provokes a pro-inflammatory EC phenotype, compensated by an enhanced CD40 shedding to neutralize excess CD40 ligand. Homozygosity for the C allele is the cause for a genetic susceptibility to atherosclerosis and its sequelae.

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