Association of matrix metalloproteinase 9 genotypes and cardiovascular disease risk factors with serum matrix metalloproteinase 9 concentrations in Taiwanese individuals.

BACKGROUND: Circulating concentrations of matrix metalloproteinase 9 (MMP-9) are associated with cardiovascular disease mortality in patients with coronary artery disease. We investigated the determinants of MMP-9 concentrations by analyzing MMP-9 genotypes and risk factors for cardiovascular disease. METHODS: A total of 596 individuals were recruited for this study. Six single nucleotide polymorphisms (SNP) with coverage of the MMP-9 gene region were analyzed; and two genotypes, rs3918242-TT and rs2274756-AA, which were in nearly complete linkage disequilibrium, were associated with higher MMP-9 values (p=0.007 and p=0.008, respectively). In age- and gender-adjusted regression models, MMP-9 concentrations were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR) index and triglyceride concentrations, fasting serum insulin, fasting plasma glucose, C-reactive protein, fibrinogen, and serum amyloid A. By multivariate analysis, rs2274756 genotypes, age, smoking status, fibrinogen and fasting plasma glucose concentrations were all independently associated with MMP-9 (p=0.007, p=0.033, p=0.003, p=0.013, and p=0.012, respectively). CONCLUSIONS: The rs2274756-AA and rs3918242-TT genotypes, younger age, current smoking status and increased fasting plasma glucose, and fibrinogen concentrations were independently associated with high serum MMP-9 concentrations in Taiwanese individuals.

CAG repeat polymorphism of the MEF2A gene is not associated with the risk of coronary artery disease among Taiwanese.

A 21-bp deletion mutation of the exon 11 of the myocyte enhancer factor-2A (MEF2A) gene was shown to cause familial coronary artery disease. This finding raises the possibility that MEF2A variants may contribute to the risk of coronary artery disease. In total, 258 patients with coronary artery disease and 258 controls were analyzed for the MEF2A variants. The analysis revealed that all patients were negative for Pro279Leu and 21-bp deletion mutations in exons 7 and 11, respectively. The distribution of the allele frequencies of MEF2A exon 11 CAG repeat (CAG)n polymorphism was similar in both patients and controls; Further, no significant association was noted between MEF2A exon 11 (CAG)n polymorphism and the risk of myocardial infarction. Our data suggest that there is no evidence of an association between the MEF2A exon 11 (CAG)n polymorphism and the risk of coronary artery disease/myocardial infarction in the Chinese population in Taiwan.

The PCSK9 gene E670G polymorphism affects low-density lipoprotein cholesterol levels but is not a risk factor for coronary artery disease in ethnic Chinese in Taiwan.

BACKGROUND: An E670G polymorphism of the exon 12 of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene was recently found to be associated with increased plasma low-density lipoprotein cholesterol (LDL-C) levels and severity of coronary atherosclerosis. This case-control study tested for a possible link between this PCSK9 polymorphism and the risk of coronary artery disease (CAD) in an ethnic Chinese population in Taiwan. METHODS: The subjects included 202 CAD patients and 614 unrelated controls. Genotypes were determined via polymerase chain reaction, restriction mapping with MboII, and gel electrophoresis. RESULTS: Contradictory to the results of a previous report, a significantly lower level of LDL-C was noted in 670G carriers than in non-carriers (2.78+/-0.82 mmol/L vs. 3.02+/-0.85 mmol/L; p=0.029) among controls, after adjusting for age, gender, smoking, hypertension, diabetes mellitus, body mass index, and use of lipid-lowering agents. The 670G carrier was identified less frequently in patients with CAD than in controls (9.9% vs. 11.9%), but the difference was not significant in a multivariable logistic regression analysis (odds ratio=0.73; 95% CI=0.24-2.22; p=0.575). The G allele also occurred at similar frequencies in the two groups (5.0% vs. 6.0%; p=0.421). CONCLUSIONS: These results indicate that the E670G polymorphism of the PCSK9 gene modulates plasma LDL-C levels, but that it is not a risk variant for CAD in ethnic Chinese in Taiwan.

Apolipoprotein A5 gene -1131T/C polymorphism is associated with the risk of metabolic syndrome in ethnic Chinese in Taiwan.

BACKGROUND: The -1131T>C polymorphism in the apolipoprotein gene A5 (APOA5) was found to be associated with increased levels of plasma triglyceride and decreased levels of high-density lipoprotein cholesterol (HDL-C), which are characteristic dyslipidemic components of metabolic syndrome. This study aimed to identify a link between this polymorphism and the risk of metabolic syndrome. METHODS: The sample population comprised 615 unrelated subjects, 18.7% of whom had metabolic syndrome. Genotypes were determined via polymerase chain reaction, restriction mapping with MseI, and gel electrophoresis. RESULTS: A significantly higher level of triglycerides and a lower level of HDL-C were noted in carriers of the -1131C allele than in the non-carriers (p<0.001 and p=0.044, respectively). The frequency of the -1131C allele in the metabolic syndrome-affected subjects was significantly higher than that of the group of unaffected subjects (37.4% vs. 27.7%, p=0.004). Even after adjusting for age, gender, smoking, regular exercise, and waist-to-hip ratio, the APOA5 -1131C allele carriers remained significantly associated with an increased risk of metabolic syndrome (OR=1.77, 95% CI, 1.13-2.77; p=0.012). CONCLUSIONS: These results indicate that the association of APOA5 -1131T>C polymorphism with dyslipidemia can also contribute to an increased susceptibility to metabolic syndrome in the Chinese, as a result of its effect on triglyceride metabolism.

Association between P478S polymorphism of the filaggrin gene and risk of psoriasis in a Chinese population in Taiwan.

Abnormal keratinocyte terminal differentiation is one of the important characteristics of psoriatic lesions. Filaggrin (FLG) is a key protein that facilitates the terminal differentiation of the epidermis. Thus, FLG genetic variants may modify the risk of psoriasis. In total, 314 patients with psoriasis and 611 control subjects were analyzed for the presence of FLG R501X, 2282del4 mutations, and P478S (rs11584340, C/T base change) polymorphism by polymerase chain reaction (PCR). The analysis revealed that both the R501X and 2282del4 mutations were not present in a subset of 200 patients (64%) with psoriasis. In contrast, a marginally significant difference (P = 0.020) was found in the distribution of rs11584340 genotype frequencies between psoriatic patients and controls. The frequency of the TT genotype in psoriasis patients was significantly higher than in controls (37.9% vs. 29.1%, respectively, P = 0.007). The T allele frequency of patients (60.5%) was also significantly higher than that of controls (53.9%) (P = 0.007). After adjusting for age and gender, carriers of the TT genotype were 1.46 (95% CI, 1.08-1.96) times more likely than non-carriers to have psoriasis (P = 0.013). In conclusion, our results suggest that FLG P478S polymorphism may confer susceptibility to the development of psoriasis among Taiwanese Chinese.

Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease among Chinese in Taiwan.

Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case-control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P<0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P=0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P=0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07-3.00; P=0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese.