The augmented endothelium-dependent vasodilation of the forearm resistance vasculature does not support the presence of endothelial dysfunction in young SNP carriers and indicates that other mechanisms are responsible for the strong association between coronary artery diseases and the rs9818870 polymorphism, located on 3q22.3.
Aim was to estimate the genotypic distribution and risk allele frequencies of 13 Coronary Artery Disease (CAD) risk Single Nucleotide Polymorphisms in loci identified by the CARDIoGRAMplusC4D consortium namely MIA3 rs17465637; 9p21 rs10757274; CXCL12 rs1746048; APOA5 rs662799; APOB rs1042031; LPA rs3798220; LPA 10455872; MRAS rs9818870; LPL rs328; SORT1 rs646776; PCSK9 rs11591147; APOE rs429358; APOE rs7412 in Pakistani PCAD patients and controls.
In the current study, locus C12orf43/rs2258287 was found to be associated with the risk of CAD in the studied Pakistani cohort (OR 0.18; CI 0.08-0.37; p = 0.0001) while no association was observed for MRAS/rs9818870 (OR 1.34; CI 0.65-2.76; p = 0.42).
We selected 1920 CAD patients and healthy participants from Han Chinese and genotyped 22 single nucleotide polymorphisms (SNPs) spanning 150 kilobases (kb) chromosomal region flanking rs9818870, a SNP associated with CAD at 3q22.3 in Caucasian.
Our results revealed that an intron SNP, rs1199337, tends to be marginally associated with CAD as previously reported in Caucasians (nominal P=0.01, OR 1.10, 95% CI 1.01-1.20).
p.Gly23Val-MRAS is both necessary and sufficient to elicit a cardiac hypertrophy phenotype in iPSC-CMs that includes increased cell size, changes in cardiac gene expression, and abnormal calcium handling-providing further evidence to establish the monogenetic pathogenicity of p.Gly23Val-MRAS in NS with cardiac hypertrophy.
Interestingly, rs253662 (p = 0.014) and rs6782181 (p = 0.019) were protective against acquiring high low-density lipoprotein-cholesterol (hLDL-chol) levels (p = 0.014), while rs1720819 showed similar effects against CAD (p < 0.0001).
Interestingly, rs253662 (p = 0.014) and rs6782181 (p = 0.019) were protective against acquiring high low-density lipoprotein-cholesterol (hLDL-chol) levels (p = 0.014), while rs1720819 showed similar effects against CAD (p < 0.0001).
In relation to lipid profile, rs40593, rs751357, rs6782181 were associated with increased total cholesterol (TC) levels.Summarily, this study suggested that MRAS rs40593 may contribute to the increased risk of area of cerebral infarction of IS in Han population. rs40593, rs751357, and rs6782181 were associated with higher serum TC levels.
The rs6782181_GG also conferred risk for obesity (1,764 cases vs. 2,586 controls) [1.16(1.03-1.30); p = 0.017], hypercholesterolaemia (1,686 vs. 2,744) [1.23(1.02-1.47); p = 0.019], hypertriglyceridaemia (1,155 vs. 3,496) [1.29(1.01-1.45); p = 0.043] and low high-density lipoprotein-cholesterol (lHDL-chol) levels (1,935 vs. 2,401) [1.15(1.02-1.30); p = 0.023] after adjustment.
The rs6782181_GG also conferred risk for obesity (1,764 cases vs. 2,586 controls) [1.16(1.03-1.30); p = 0.017], hypercholesterolaemia (1,686 vs. 2,744) [1.23(1.02-1.47); p = 0.019], hypertriglyceridaemia (1,155 vs. 3,496) [1.29(1.01-1.45); p = 0.043] and low high-density lipoprotein-cholesterol (lHDL-chol) levels (1,935 vs. 2,401) [1.15(1.02-1.30); p = 0.023] after adjustment.
Among the studied SNPs, rs6782181 (p = 0.017) and rs9818870T (p = 0.009) were associated with CAD following adjustment for sex, age and other confounding risk factors.
The rs6782181_GG also conferred risk for obesity (1,764 cases vs. 2,586 controls) [1.16(1.03-1.30); p = 0.017], hypercholesterolaemia (1,686 vs. 2,744) [1.23(1.02-1.47); p = 0.019], hypertriglyceridaemia (1,155 vs. 3,496) [1.29(1.01-1.45); p = 0.043] and low high-density lipoprotein-cholesterol (lHDL-chol) levels (1,935 vs. 2,401) [1.15(1.02-1.30); p = 0.023] after adjustment.
In relation to lipid profile, rs40593, rs751357, rs6782181 were associated with increased total cholesterol (TC) levels.Summarily, this study suggested that MRAS rs40593 may contribute to the increased risk of area of cerebral infarction of IS in Han population. rs40593, rs751357, and rs6782181 were associated with higher serum TC levels.
In relation to lipid profile, rs40593, rs751357, rs6782181 were associated with increased total cholesterol (TC) levels.Summarily, this study suggested that MRAS rs40593 may contribute to the increased risk of area of cerebral infarction of IS in Han population. rs40593, rs751357, and rs6782181 were associated with higher serum TC levels.
The augmented endothelium-dependent vasodilation of the forearm resistance vasculature does not support the presence of endothelial dysfunction in young SNP carriers and indicates that other mechanisms are responsible for the strong association between coronary artery diseases and the rs9818870 polymorphism, located on 3q22.3.
These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in individuals free of overt heart disease.
The augmented endothelium-dependent vasodilation of the forearm resistance vasculature does not support the presence of endothelial dysfunction in young SNP carriers and indicates that other mechanisms are responsible for the strong association between coronary artery diseases and the rs9818870 polymorphism, located on 3q22.3.
MRAS gene marker rs9818870 is not associated with acute coronary syndrome in the Czech population and does not predict mortality in males after acute coronary syndrome.