Abstract
ObjectiveTo explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population.MethodsA cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini's Score System and counts of diseased vessels.ResultsGensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup).ConclusionsAllele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.
Highlights
Coronary artery disease (CAD) is predicted to be the most common cause of death globally, including in China, by 2020, when the 10 leading causes of disability-adjusted life-years are projected to be ischaemic heart disease [1], In addition to lifestyle and environmental factors, which are major aetiologic determinants, multiple combinations of gene–gene and gene–environment interactions play a key role in the development of CAD [2,3]
Genotype distribution of rs6903956 polymorphisms in subjects grouped by diseased vessel count
We all know that CAD is associated with hypertension, obesity, low high-density lipoprotein-cholesterol (HDL-C) levels and diabetes mellitus (DM) [12,13,14,15,16]
Summary
Coronary artery disease (CAD) is predicted to be the most common cause of death globally, including in China, by 2020, when the 10 leading causes of disability-adjusted life-years (in descending order) are projected to be ischaemic heart disease [1], In addition to lifestyle and environmental factors, which are major aetiologic determinants, multiple combinations of gene–gene and gene–environment interactions play a key role in the development of CAD [2,3]. The heritability of CAD is estimated to be 40 to 60%, the mechanism of genetic is still little known [4]. A number of genomic regions, variants in candidate genes, and risk factors were implicated in increasing the susceptibility of CAD [5]. The most robust genetic risk variant for CAD was identified on chromosome 9p21.3 by genome-wide association studies (GWAS) [6]. The first GWAS for CAD in a Chinese Han population had identified rs6903956, which is in C6orf105 on chromosome 6p24.1, to be significantly associated with susceptibility to CAD [7]
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