The Relationship between Serum Retinol-Binding Protein 4 Levels and Coronary Artery Disease in Korean Adults / 당뇨병

BACKGROUND: A recently discovered adipokine, retinol-binding protein-4 (RBP-4), is reportedly associated with insulin resistance and metabolic syndrome. This study was performed to analyze the relationship between serum RBP-4 levels and coronary artery disease (CAD) in Korean adults. METHODS: In 235 subjects (mean age 58 years) in whom coronary artery angiograms were performed due to complaints of chest pain, serum RBP-4 levels were measured by enzyme-linked immunosorbent assay. Coronary artery angiograms were performed in all subjects and the severity of CAD was assessed by the number of stenotic vessels. The presence of metabolic syndrome was defined by AHA/NHLBI criteria with body mass index substituted for waist circumference. RESULTS: Coronary angiogram showed that 101 subjects (43%) had normal coronary vessel, 82 subjects (34.9%) had 1-vessel disease, 31 subjects (13.2%) had 2-vessel disease and 21 subjects (8.9%) had 3-vessel disease. Subjects with coronary artery stenosis showed a higher mean age (60.5 +/- 10.0 years), fasting glucose (123.3 mg +/- 45.0 mg/dL) and lower mean value for high-density lipoprotein cholesterol (HDL-C) level (49.0 +/- 13.2 mg/dL), although serum RBP-4 levels were not significantly different between those with and without CAD. Mean age and fasting glucose level increased significantly as the number of stenotic vessels increased, although serum RBP4 level showed no significant differences among the different groups. Among the metabolic parameters, only serum triglyceride levels showed a significant correlation with serum RBP-4 levels. CONCLUSION: There was no difference in mean serum RBP-4 levels between subjects with or without coronary artery disease in Korean adults. Further studies are warranted to draw a clear conclusion on the effect of RBP-4 on atherosclerosis.

Association between two SNPs (+45T>G and +276G>T) of the adiponectin gene and coronary artery diseases / 대한내과학회지

BACKGROUND: Adiponectin, an adipocyte-secreted protein, is known to have anti-atherogenic, anti-inflammatory and anti-diabetic properties. Adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease. Several studies have been performed aiming to investigate the association of genetic variations in the adiponectin with obesity, insulin resistance, and type 2 diabetes but few studies were performed in association with coronary artery disease. Therefore we examined the association between two single nucleotide polymorphisms (SNPs) (+45T>G and +276G>T) of the adiponectin gene and coronary artery diseases (CAD). METHODS: One hundred fifty six subjects were enrolled in which coronary angiograms were performed due to chest pain in Kangbuk Samsung Hospital from April to August, 2003 (97 males, 59 females, mean age 57.40+/-11.15 yrs). Body mass index, fasting blood glucose, lipid profiles were measured in every subject. Single nucleotide polymorphisms (SNPs) in the adiponectin gene were determined by Taqman polymerase chain reaction (PCR) method. The presence of CAD was defined as a >50% reduction of coronary artery diameter. RESULTS: Among 156 subjects, the allele frequencies were 0.683 for G allele and 0.317 for T allele in SNP +276G>T and 0.705 for T allele and 0.295 for G allele in SNP +45T>G. Both genotypes were in compliance with Hardy-Weinberg equlibrium. Mean serum fasting glucose level was significantly higher and mean high-density lipoprotein cholesterol (HDL-C) level was lower in CAD groups (p=0.015, p=0.004). No association with the presence of CAD was observed for adiponectin gene SNP276 and SNP45 (p=0.954, p=0.843). Also, no significant association was observed between the severity of CAD and either SNPs (p=0.571, p=0.955). CONCLUSIONS: Our study showed that SNP +276G>T and +45T>G in adiponectin gene were not associated with the presence of CAD. Further studies will be necessary to confirm the role of SNP 276G>T and 45T>G in the development of CAD.

The association of KLOTHO gene polymorphism with coronary artery disease in Korean subjects / 대한내과학회지

BACKGROUND: Klotho knock-out mouse is being thought as a good animal model for human aging and these mice show typically severe atherosclerosis of large arteries. Recent studies report on the association of KLOTHO gene mutation with cardiovascular diseases in humans. We observed the frequencies of G395A in promoter and C1818T in exon 4 of KLOTHO gene and investigated their relationships with the presence of coronary artery disease (CAD) in those patients underwent coronary angiograms METHODS: Total 168 subjects (mean age 58 years, 26-87 years) who underwent coronary angiograms due to chest pain were enrolled and blood pressure, body mass index, fasting blood glucose and lipid profiles were measured in all subjects. Genotypings were performed with real-time polymerase chain reaction from sampled blood. RESULTS: The allele frequencies of G395A were 0.872 for G allele and 0.128 for A allele and those of C1818T were 0.830 for C allele and 0.170 for T allele. Both were in compliance with Hardy-Weinberg equilibrium (p=0.99, p=0.82). When the subjects were classified into four groups according to the number of stenotic vessels, there were no differences among the mean values of the cardiovascular risk factors, except high-density lipoprotein cholesterol, that showed a significant difference between that of normal and the diseased vessel groups. There were no differences in the prevalence of CAD according to the genotypes of G395A polymorphism, but for C1818T polymorphism, subjects with T allele showed lower prevalence of CAD than those with CC genotype. When the subjects were divided into two groups according to age, in the group under 60 years of age, T allele carriers of C1818T polymorphism showed lower prevalence of CAD than non-carriers. In the group older than 60 years, A allele carriers of G395A polymorphism showed lower prevalence of CAD than non-carriers. CONCLUSIONS: The frequencies of KLOTHO G395A and C1818T polymorphisms in Koreans were observed similarly to those reported in other Asian races and the phenotypic expression on CAD was different according to age groups. These results infer the possibility of KLOTHO gene as the candidate gene of atherosclerosis in humans, which needs further research.

Association between serum osteoprotegerin levels and disease severity and cardiovascular risk factors in patients with coronary artery diseases / 대한내과학회지

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein that acts as a decoy receptor to receptor-activated RANKL (receptor-activated NF-kappa B ligand) and inhibits the differentiation of osteoclasts. OPG knock-out mice showed severe osteoporosis and aortic calcification and high serum OPG levels have been shown to predict future cardiovascular mortality in old Caucasian females. We measured serum OPG levels in coronary artery disease patients, compared serum OPG levels among different groups according to the number of stenotic vessels and observed the correlation with aortic calcification and cardiovascular risk factors. METHODS: One hundred subjects were enrolled in which coronary angiograms were performed due to chest pain in Kangbuk Samsung Hospital from April to August, 2003 (59 males, 41 females, mean age 56.9 +/- 11.9 yrs). Blood pressure, body mass index, fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels were measured in every subject. Cardiac echocardiograms were checked in 82 subjects and left ventricular mass indices (LV mass index) were calculated. Serum OPG levels were measured with enzyme-linked immunosorbent assay (ELISA) method. The presence of calcifications in aortic knob was checked in simple chest X-ray. RESULTS: Subjects were divided in 4 groups according to the number of stenotic vessels (significant stenosis>or=50%); 45 subjects in normal group, 30 in 1-vessel disease group, 15 in 2-vessel disease group and 10 in 3-vessel disease group. Mean value for age was significantly different among groups (p<0.01). Mean serum HDL-cholesterol level of normal group was higher than that of 1-vessel disease or 2-vessel disease group (p<0.05). Serum OPG levels increased significantly as the number of stenotic vessels increased and in post-hoc analysis, mean serum OPG levels were higher in 3-vessel disease group than normal or 1-vessel disease groups (p<0.05). Age, LV mass index and number of stenotic vessels showed significantly positive correlation with serum OPG levels, although only number of stenotic vessels showed persistently significant correlation after adjustment for age. There were no differences of serum OPG levels according to the presence of fasting hyperglycemia or aortic calcifications. CONCLUSION: Serum OPG levels increased as the number of stenotic coronary arteries increased and showed positive relationships with age, LV mass index. OPG seems to be elevated as a compensatory mechanism to the progression of atherosclerosis in humans.