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CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P<0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P=3.9×10-4 and interaction P=0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Recently, genome-wide association studies identified a novel psoriasis susceptibility locus tagged by two single-nucleotide polymorphisms (SNPs) rs4795067 and rs28998802, both of which are in the intronic region of inducible nitric oxide synthase ( iNOS) gene. This study aimed to assess the role of (CCTTT) pentanucleotide repeat polymorphisms in the promoter region of iNOS gene in Chinese-Taiwanese patients with psoriasis. In total, 280 patients with psoriasis and 512 control subjects were analyzed for the presence of the iNOS microsatellite polymorphism by polymerase chain reactions. The alleles were classified as S and L alleles according to the number of (CCTTT) repeats, with the alleles with ≤13 repeats designated as S and alleles with ≥14 repeats designated as L alleles. The distribution of allele frequencies and genotypes was significantly different between the control and psoriasis groups ( P = 0.040, and 0.014, respectively). After adjustment for age, sex, body mass index, smoking, diabetes, and hypertension, carriers of the LL genotype were 0.38 (95 % confidence interval 0.16-0.95) times less likely than non-carriers to have psoriasis ( P = 0.038). The promoter assays demonstrated that the iNOS promoter activity increases in parallel with the repeat number of (CCTTT) in HaCaT cells. Approximately 70 % of the study subjects were genotyped for rs4795067 and rs28998802. The rs4795067 is in linkage disequilibrium with the microsatellite L/S allelic classification. The association of iNOS microsatellite with psoriasis is independent of these known iNOS variants. Our results suggest that the iNOS microsatellite may contribute to the genetic background of psoriasis in Chinese-Taiwanese patients. [ABSTRACT FROM AUTHOR]

Dilated inferior vena cava (IVC) is prevalent among patients with heart failure (HF), but whether its presence predicts worsening renal function (WRF) or adverse outcomes is unclear. This cohort study analyzed patients with left ventricular ejection fraction <40 % and repeated hospitalizations (≥2 times) for HF between August 2009 and August 2011. The study endpoints were death and HF re-hospitalization. Among baseline parameters, IVC diameter was the most powerful predictor for the development of WRF (area under the curve = 0.795, cut-off value = 20.5 mm). During the 2-year follow-up, 36 patients (49 %) were re-hospitalized for HF and 14 patients (19 %) died. The event rates were significantly greater in the WRF group than in the non-WRF group (71 vs. 30 %, P < 0.001 for HF re-hospitalization; 29 vs. 10 %, P = 0.03 for death). In Cox regression model, the risk of combined end-points was increased in patients with aging, elevated blood urine nitrogen, IVC >21 mm, and WRF. When adjusted for confounding factors, IVC >21 mm [hazard ratio (HR) 3.73, 95 % confidence interval (CI) 1.66-8.34] and WRF (HR 2.68, 95 % CI 1.07-6.75) were significant predictors for adverse outcomes. In patients with advanced decompensated HF, dilated IVC (>21 mm) predicted the development of WRF and could be a predictor for adverse outcomes. [ABSTRACT FROM AUTHOR]

Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96-149.26, p = 0.002; OR 0.92, 95 % CI 0.86-0.99, p = 0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49 ± 28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09-3.24, p = 0.024; HR 1.82, 95 % CI 1.09-3.03, p = 0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic disease characterized by inflammation of the skin. The expression of heme oxygenase-1 (HO-1), the rate-limiting enzyme involved in heme degradation, correlates well with the severity of psoriasis, and is a heritable trait. This study aimed to assess the role of (GT) dinucleotide repeat polymorphisms in the promoter region of the HO- 1 gene in Chinese-Taiwanese patients with psoriasis. In total, 288 patients with psoriasis and 542 control subjects were analyzed for the presence of the HO- 1 microsatellite polymorphism by using polymerase chain reaction. The alleles were classified as the S and L alleles according to the number of (GT) repeats, with the alleles with ≤26 repeats designated as S and alleles with ≥27 repeats designated as L alleles. The subjects were then classified as having S/S, S/L, or L/L genotypes according to each of their HO- 1 alleles. No significant difference was observed in either the genotype or allele distribution between the patients and healthy controls. However, the average number of repeats of both alleles in psoriasis patients with late disease onset was lower than that of psoriasis patients with early disease onset (26.7 ± 3.2 vs. 27.5 ± 3.4; P = 0.043, adjusted for age and sex), but the difference was not significant after additional adjustment for body mass index, smoking, diabetes, and hypertension ( P = 0.189). Our results suggest that the HO- 1 microsatellite polymorphism may not contribute to the genetic background of psoriasis in Chinese-Taiwanese patients. [ABSTRACT FROM AUTHOR]

ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between ABCG5/G8 gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 Taiwan Biobank participants with whole-genome sequencing data and 117,679 participants with Axiom Genome-Wide CHB Array data were enrolled for analysis. Using genotype–phenotype and stepwise linear regression analyses, we found independent associations of four Asian-specific ABCG5 variants, rs119480069, rs199984328, rs560839317, and rs748096191, with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels (all p ≤ 0.0002). Four other variants, which were in nearly complete linkage disequilibrium, exhibited genome-wide significant associations with gallstone disease history, and the ABCG8 rs11887534 variant showed a trend of superiority for gallstone disease history in a nested logistic regression model (p = 0.074). Through regional association analysis of various other cardiometabolic traits, two variants of the PLEKHH2, approximately 50 kb from the ABCG5/G8 region, exhibited significant associations with blood pressure status (p < 10−6). In conclusion, differential effects of ABCG5/G8 region variants were noted for lipid profile, blood pressure status, and gallstone disease history in Taiwan. These results indicate the crucial role of individualized assessment of ABCG5/G8 variants for different cardiometabolic phenotypes. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic disease characterized by inflammation of the skin. The level of C-reactive protein (CRP), an inflammatory marker that correlates well with the severity of psoriasis, is a heritable trait. This study aimed to assess the role of variations in the CRP gene in patients with psoriasis among the Chinese-Taiwanese. In total, 305 patients with psoriasis and 615 control subjects were analyzed for the presence of the CRP polymorphisms rs2794521, rs3091244, and rs1800947 by polymerase chain reaction. The analysis revealed that neither polymorphism was found to be associated with psoriasis. No significant difference was observed in the genotype and allele distribution for any of the individual CRP polymorphisms between the cases and the controls. The overall haplotype frequency profiles derived from the three polymorphisms did not differ significantly between the cases and the controls. Our results suggest that these three CRP gene polymorphisms may not contribute to the genetic background of psoriasis in Chinese-Taiwanese. [ABSTRACT FROM AUTHOR]

Objectives: Endothelin-1 (ET-1) induces cardiac hypertrophy, whereas adiponectin may elicit protective effects in the vasculature and myocardium. We therefore evaluated the relationship between plasma ET-1 and adiponectin levels in heart failure (HF) patients, and the association between adiponectin expression and ET-1-induced hypertrophy of human cardiomyocytes (HCM) in vitro. Methods: One hundred seventeen patients with chronic HF were enrolled into this study. A group of 7 patients with end-stage HF undergoing heart transplantation was included in the histopathological study. Baseline clinical evaluations and laboratory measurements were performed. HCM cultures were studied to investigate the effect of ET-1 on cell size and adiponectin expression. Results: Plasma ET-1, adiponectin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased with the severity of HF. Higher New York Heart Association functional class, plasma ET-1, adiponectin, and NT-proBNP levels were significant predictors of adverse outcomes in these patients. The myocardial expression of adiponectin was significantly higher in the recipient hearts of patients undergoing emergency or urgent heart transplantation. In cell culture, ET-1 significantly increased cell size and adiponectin expression in HCM. Conclusions: Adiponectin was significantly elevated in HF and was significantly associated with ET-1. The study provides a basis for further investigation of ET-1 and adiponectin modulation as a therapeutic strategy for ventricular remodeling in HF. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective: ATF3 has traditionally been related to various inflammatory processes. Our aim was to test the statistical association between variations in the ATF3 gene and levels of nine serum inflammatory markers, including C reactive protein (CRP), in a Taiwanese population using interaction analysis. Methods: A sample population of 604 Taiwanese subjects was enrolled. Five tagging single nucleotide polymorphisms of the ATF3 gene from the Han Chinese HapMap Database were selected and genotyped. Results: With or without adjustment for clinical covariates, ATF3 genotypes were found to be associated with CRP levels but not with other inflammatory marker levels. Minor alleles of 2 of the 5 ATF3 SNPs were associated with decreased CRP levels predominantly in non-obese subjects (Bonferoni P =0.018, and P =0.002 for rs11571530, and rs10475, respectively). Two haplotypes inferred from the 5 SNPs, GATTA and TACCA, were also associated with increased or decreased CRP levels, respectively, in non-obese subjects (Bonferoni P =0.012 and P =0.01, respectively) but not in obese subjects. Interaction analysis revealed interaction of obesity with an ATF3 genotype associated with a high CRP level (interaction P =0.006 for SNP rs10475). An effect of obesity on CRP level was also noted in haplotype interaction analysis (interaction P =0.019 for haplotype TACCA). Conclusions: ATF3 polymorphisms are independently associated with CRP levels in Taiwanese subjects. Further, ATF3 genotypes/haplotypes interact with obesity to set CRP levels. These findings may have implications for the prediction of atherosclerotic disease. [Copyright &y& Elsevier]

Abstract: Background: The level of C-reactive protein (CRP), an inflammatory biomarker that predicts future cardiovascular events, is a heritable trait that has been associated with variants of CRP and hepatic nuclear factor-1α (HNF1A) genes. Our aim was to test the statistical association between HNF1A genotypes/haplotypes and serum CRP level in Taiwanese. Methods: A sample population of 617 Taiwanese subjects (all Han-Chinese origin) was enrolled. Five HNF1A single nucleotide polymorphisms (SNPs) rs1920792, rs1169288, rs7310409, rs2464196, rs1169310 were genotyped and analyzed. Results: After adjusting for clinical covariates, minor alleles of all the 5 study SNPs were associated with decreased CRP level (P =0.0078, P= 0.0107, P= 0.0006, P= 0.0004 and P= 0.0003, respectively). A common haplotype (TGATA) tagged by the minor alleles of study SNPs was associated with significantly decreased CRP level (P =0.0112). Subgroup analysis revealed that the association between HNF1A genotypes and CRP level occurred only in non-obese subjects. Conclusions: HNF1A polymorphisms are independently associated with CRP level in Taiwanese. Further, HNF1A genotypes interact with obesity to set CRP level, revealing that genetic determinants for CRP level may be different between obese and non-obese individuals. [Copyright &y& Elsevier]

An insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene accounts for 50% of the interindividual serum ACE level variation. Because the renin—angiotensin system regulates coagulation and vasoconstriction, it could have a role in venous thromboembolism (VTE). Several studies have evaluated the relationship between ACE I/D polymorphism and VTE, although the findings have been controversial. We performed a meta-analysis by pooling data from 14 studies. Publication bias was not observed. The current study did not support any association between the DD genotype and VTE. The pooled odds ratio (ORp) was 1.206; 95% confidence interval (CI), 0.951-1.531; P = .123. Similar results were obtained when the effects of the D allele were assumed to be dominant (DD and ID vs II; ORp = 1.127, 95% CI, 0.902-1.409). Our data do not support the inclusion of ACE I/D polymorphism testing in clinical thrombophilia workups until more compelling data are made available. [ABSTRACT FROM PUBLISHER]

Abstract: Although inflammation has been shown to play an important role in metabolic syndrome (MetS), the association between inflammatory marker gene polymorphisms and the risk of MetS has not been fully elucidated. This study was initiated to investigate the association between functional variants of inflammatory marker genes and the risk of MetS in Taiwanese adults. The sample population comprised 615 unrelated subjects, of which 22% had MetS. The single nucleotide polymorphisms rs5491 on the intercellular adhesive molecule 1 (ICAM1) gene and rs3091244 on C-reactive protein (CRP) were genotyped. The ICAM1 rs5491 polymorphism was significantly associated with the level of soluble intercellular adhesive molecule 1 (P < .001). Both the ICAM1 rs5491 and the CRP rs3091244 were shown to have significant association with MetS after adjustment for age, sex, smoking, and body mass index, but not after adjustment for levels of the respective serum marker. Independent associations between the combined ICAM1-CRP (rs5491 and rs3091244) genotypes and MetS were found by multivariate analysis (P = .005). In subgroup analysis, association of combined genotypes with insulin resistance and MetS mainly occurred in subjects with central obesity. In conclusion, inflammatory marker gene polymorphisms play an important role in modulating the risk of insulin resistance and MetS for subjects with central obesity. These findings will contribute toward a better understanding of the mechanism of association between inflammatory markers and the risk of developing atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Although percutaneous transluminal angioplasty (PTA) is an effective therapeutic procedure for critical limb ischemia, several clinical factors can influence the outcome of PTA for peripheral arterial disease (PAD). The aim of this study is to identify the outcome predictors of PTA in infected diabetic foot patients with PAD. Methods: Eighty-five diabetic patients with a total of 90 infected limbs treated by PTA participated in this study. Patients were initially admitted for infected foot ulcers and were later diagnosed with PAD. Even though all patients underwent successful PTA within 15 days of admission, limb salvage was successful in 66 cases while 24 underwent subsequent amputation. The clinical characteristics and laboratory variables of both groups before PTA were compared and analyzed. Results: Significantly higher level of C-reactive protein (CRP) was observed in the major amputation group before PTA. The cutoff value via receiver operating characteristic curve was 50mg/L (81.8% specificity, 70.7% sensitivity). Multivariate logistic regression analysis revealed that CRP levels may serve as valuable marker in determining a successful outcome. Conclusion: Reduced CRP levels (<50mg/L), which indicates a low infection severity, may serve as a major predictor of successful PTA outcome in diabetic patients with infected foot ulcers. [ABSTRACT FROM AUTHOR]

Background: In atrial fibrillation (AF), left ventricular (LV) systolic function positively correlates with the ratio of the preceding to prepreceding RR intervals (RRp/RRpp) and single-beat determination of LV function at a beat with equal RRp and RRpp closely estimates the average value over all cardiac cycles. The study was designed to evaluate the feasibility of single-beat determination that was based on the ratio of RRp/RRpp to accurately assess RV function in AF. Methods: In 60 patients with AF, RV fractional area change (RVFAC), RRp and RRpp were measured during 20 beats for each patient. The relationship between RVFAC and RRp/RRpp was evaluated by linear regression analysis. The measured values of RVFAC at the beats with equal RRp and RRpp were compared with the average values over 20 beats. The influence of RRp cycle lengths on the values of RVFAC at the beats with equal RRp and RRpp was examined from the plot of normalized value against RR intervals. Results: There were a positive linear relationship between RVFAC and RRp/RRpp in all patients (P < 0.001 in all). The RVFAC measured by single-beat method and cycle lengths <500 ms were usually far below the average values. After excluding beats with cycle lengths <500 ms, RVFAC determined by single-beat method was very close to the average values (y = 0.96x + 1.91%, r = 0.961; P < 0.001; bias 0.26%). Conclusions: RV FAC correlates positively with RRp/RRpp and single-beat determination of RV function is feasible and accurate in patients with chronic AF. (Echocardiography 2010;27:1188-1193) [ABSTRACT FROM AUTHOR]

Abstract: Background: Acid-sensing ion channel 3 (ASIC3) is a ligand-gated cation channel activated by extracellular protons. ASIC3−/− mice exhibit protection against age-dependent glucose intolerance with enhanced insulin sensitivity. Methods: To determine the association between ASIC3 genetic polymorphisms and insulin resistance in Taiwanese, 606 unrelated subjects with no history of cardiovascular disease were recruited during routine health examinations. Results: Six ASIC3 gene polymorphisms were genotyped and only the rs2288646 polymorphism was found associated with insulin resistance. Significantly lower fasting serum insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) index and significantly higher quantitative insulin sensitivity check index (QUICKI) were observed in subjects carrying the rs2288646-A allele than in the non-carriers (P =0.028, P =0.047 and P =0.031, respectively) after adjustment for age, gender, and body mass index (BMI). Significantly lower frequencies of the rs2288646-A-containing genotypes were found in insulin resistant subjects (P =0.023). By multivariate analysis, rs2288646 genotypes, age, BMI, fasting plasma glucose level, C-reactive protein level, and soluble intercellular adhesive molecule 1 level, were all independently associated with HOMA-IR index and QUICKI (all, P <0.05). Conclusions: Our analysis indicated an independent association between an ASIC3 genetic polymorphism and insulin resistance in Taiwanese. [Copyright &y& Elsevier]

Abstract: Insulin resistance, which plays a fundamental role in the pathogenesis of metabolic syndrome and type 2 diabetes mellitus, is associated with serum levels of inflammatory markers and abdominal obesity. Whether insulin resistance is caused by inflammation or is an epiphenomenon of obesity remains unresolved. We therefore conducted a cross-sectional study to investigate whether the association between insulin resistance and C-reactive protein (CRP) levels is independent of abdominal obesity in a nondiabetic Taiwanese population. The study included 574 Taiwanese participants (300 men and 274 women) who were nondiabetic persons with CRP levels not exceeding 10 mg/L and who did not have a history of cardiovascular disease or were taking medication for dyslipidemia. All participants were of Han-Chinese origin. The degree of insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4). Blood pressure, fasting glucose level, triglycerides level, waist circumference, and HOMA-IR were all found to be significantly higher in Q3 and Q4 than in Q1 and Q2. Stratified analysis by sex and abdominal obesity showed that HOMA-IR was significantly associated with CRP levels in both sexes in either obese or nonobese populations. Multiple linear regression analysis adjusting for age, smoking, components of metabolic syndrome, and waist circumference showed that the association between HOMA-IR and CRP levels remained significant in both men and women (P = .029 for men and P < .001 for women). These findings confirm that insulin resistance is strongly associated with CRP levels independent of abdominal obesity in nondiabetic Taiwanese. Factors other than abdominal obesity, such as polymorphisms in the CRP gene, may influence the association of insulin resistance with CRP levels in different ethnic populations. [Copyright &y& Elsevier]

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. Clin Chem Lab Med 2010;48:543–9. [ABSTRACT FROM AUTHOR]

Abstract: Circulating concentrations of soluble cell adhesive molecules are useful predictors for the risk of development and progression of atherosclerosis. This study was initiated to investigate the association between soluble intercellular adhesive molecule–1 (sICAM-1) levels and traditional and emerging cardiovascular risk factors, as well as insulin resistance and metabolic syndrome, in a Taiwanese population. Six hundred nine unrelated individuals recruited during routine health examinations were enrolled for the analysis. In age- and sex-adjusted regression models, sICAM-1 levels were negatively associated with high-density lipoprotein cholesterol levels and positively associated with systolic, mean, and diastolic blood pressure; body mass index; waist circumference; waist-hip ratio; the homeostasis model assessment index; fasting serum insulin; triglyceride; and C-reactive protein levels. The sICAM-1 levels were also higher in subjects with current smoking (P = .001), diabetes mellitus (P = .004), insulin resistance (P < .001), and metabolic syndrome (P < .001). The sICAM-1 levels increased in a stepwise fashion with increasing Framingham risk score quartiles (P = .001) and with increasing number of metabolic syndrome components (P < .001). In subjects with metabolic syndrome, increased C-reactive protein levels were associated with increased sICAM-1 levels (P = .003). In stepwise linear regression models, sICAM-1 levels remained associated with current smoking, insulin resistance, and metabolic syndrome. In conclusion, our data revealed that insulin resistance and metabolic syndrome were associated with sICAM-1 levels in Taiwanese. These data provide further evidence of the mechanisms of sICAM-1 as a molecular marker for atherosclerosis. [Copyright &y& Elsevier]

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. Clin Chem Lab Med 2009;47:154–8. [ABSTRACT FROM AUTHOR]

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. Clin Chem Lab Med 2008;46:1714–9. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]