TNF-α polymorphisms and coronary artery disease: association study in the Korean population.

Coronary artery disease (CAD) results from atherosclerosis, a chronic inflammatory disease mediated in part by proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), which is expressed by atherosclerotic plaques. In this study, we investigated whether TNF-α gene promoter polymorphisms affect the incidence of CAD in Koreans by genotyping. 404 Control subjects and 197 patients who previously received a coronary artery stent for the G/A, C/T, and C/A polymorphisms at position -238, -857 and -863, respectively. The G/G, G/A and A/A genotypes at position -238 occurred in 85.8%, 14.2% and 0% CAD patients and 91.8%, 7.9% and 0.3% control subjects, respectively. The G/A polymorphisms at position -238 were significantly associated with CAD when assuming a dominant model of inheritance (OR = 1.87; 95% CI = 1.10-3.20; P = 0.02), and A allele carriers had a significantly increased risk of developing CAD relative to the G allele (OR = 1.74; 95% CI = 1.04-2.92; P = 0.03). However, the polymorphisms at positions -857 and -863 were not associated with CAD. Haplotype-based analysis revealed the CAD and control groups differed significantly in the frequencies of haplotype ACC at positions -238, -857 and -863 (OR = 1.77; 95% CI = 1.05-2.98; P = 0.03). This was confirmed by multivariate analysis after adjusting body mass index and the presence of diabetes and hypertension (OR = 2.06; 95% CI = 1.15-3.68; P = 0.015). Thus, the -238A allele of TNF-α is associated with an increased risk of CAD and could be used as predictor for CAD in Koreans. Further studies are needed to elucidate the clinical implications of these findings.

Association of tumor necrosis factor-α (TNF-α) promoter polymorphisms with overweight/obesity in a Korean population.

OBJECTIVE: Obesity is characterized by the activation of an inflammatory process leading to an increase in proinflammatory cytokines and adipokines. This study was designed to investigate the genetic association between tumor necrosis factor-α (TNF-α) polymorphisms and the risk of obesity in the Korean population. METHODS: Three single nucleotide polymorphisms [G-238A (rs361525), C-857T (rs1799724), and C-863A (rs1800630)] in the promoter region of TNF-α gene were analyzed in 123 control [body mass index (BMI) between 18 and 23] and 208 overweight/obese (BMI ≥ 23) subjects. RESULTS: The mean values of BMI in the control and overweight/obese groups were 21.1 ± 1.4 and 25.4 ± 1.8, respectively. Of the three SNPs, G-238A presented a significant association with overweight/obesity in the codominant model; the frequency of the G/G genotype in the overweight/obese group was 9.3% higher than that in the control group (P = 0.0046). When control and overweight/obesity subjects were combined together and analyzed, the level of high-density lipoprotein (HDL) was significantly higher in the C-857T C/C type SNP (P < 0.05). CONCLUSIONS: The results of this study suggest that the G allele of G-238A in TNF-α gene may be a risk factor for overweight/obesity in the Korean population and that the C allele of C-857T may be an protective factor in relation to the HDL level in the general Korean population.

A polymorphism at -1607 2G in the matrix metalloproteinase-1 (MMP-1) increased risk of sudden deafness in Korean population but not at -519A/G in MMP-1.

OBJECTIVES/HYPOTHESIS: Matrix metalloproteinase-1 (MMP-1) is associated with a risk of inflammatory disease and cancer invasion. Two common etiologies for sudden deafness (SD) are circulatory disturbance and inflammation. The present study aimed to investigate whether MMP-1 polymorphisms are associated with SD. STUDY DESIGN: Case-control study. Ninety-nine Korean SD patients and 530 normal patients (controls) were used in this study. METHODS: Single nucleotide polymorphism (SNP) of MMP-1 (at -1607G/2G and -519A/G) was analyzed using the pyrosequencing method. RESULTS: At MMP-1 -1607G/2G, the distributions of 2G/2G, G/2G, and G/G genotypes in controls were 36.8%, 44.3%, and 18.9%, respectively, and in SD patients were 46.5%, 48.5%, and 5.1%, respectively. The 2G/2G genotype was found to increase the risk of SD compared with the G/G genotype (codominant model: P = .0029; recessive model: P = .0003). The 2G allele was found to increase the risk of SD compared with the G allele (P = .002). At MMP1 -519A/G, there was no statistically significant increase in the risk of SD. Among haplotypes of MMP-1 polymorphisms -1607G/2G and -519A/G, 2GA and GA were found to be associated with SD (P < .05). CONCLUSIONS: These results suggest that the 2G/2G genotype is associated with an increased risk of SD compared with the G/2G and G/G genotypes. Furthermore, the 2G allele may be a risk factor for SD.