Association of genetic variants with myocardial infarction in Japanese individuals with or without metabolic syndrome.
ABSTRACT: The etiology of metabolic syndrome (MetS) is highly complex, with both genetic and environmental factors being thought to play an important role. Although MetS has been recognized as a risk factor for myocardial infarction (MI), the genetic risk for MI in individuals with or without MetS has remained uncharacterized. We examined a possible association of genetic variants with MI in individuals with or without MetS separately. The study population comprised 4,424 individuals, including 1,918 individuals with MetS (903 subjects with MI and 1,015 controls) and 2,506 individuals without MetS (499 subjects with MI and 2,007 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of Affymetrix GeneChip Human Mapping 500K Array Set. Initial screening by the Chi-square test revealed that the C?T polymorphism (rs1794429) of LRPAP1, the A?G polymorphism (rs12373237) of LAMA3 and the A?G polymorphism (rs3782257) of NCOR2 were significantly (false discovery rate of <0.05) associated with MI for individuals with MetS, and that the C?G polymorphism (rs13051704) of TFF1 was significantly related to MI for individuals without MetS. Subsequent multivariable logistic analysis with adjustment for covariates revealed that rs1794429 of LRPAP1 (recessive model; P=0.0218; odds ratio=0.71) and rs3782257 of NCOR2 (dominant model; P=0.0057; odds ratio=1.94) were significantly associated with MI among individuals with MetS, and that rs13051704 of TFF1 (additive model; P=0.0100; odds ratio=0.55) was significantly associated with MI among individuals without MetS. The genetic variants that confer susceptibility to MI differ between individuals with or without MetS. Stratification of subjects according to the presence or absence of MetS may thus be important for personalized prevention of MI based on genetic information.
Project description:<h4>Background</h4>Recently, a -168A-->G polymorphism in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to myocardial infarction (MI).<h4>Aim</h4>To confirm the association between the MHC2TA -168A-->G polymorphism and MI and to study its putative role for microalbuminuria, the metabolic syndrome (MetS) and cardiovascular mortality.<h4>Materials and methods</h4>Using an allelic discrimination method we genotyped 11,064 individuals from three study populations: 1) 4,432 individuals from the Botnia type 2 diabetes (T2D) study, 2) 1,222 patients with MI and 2,345 control subjects participating in the Malmö Diet and Cancer study and comprising an MI case-control sample, and 3) 3,065 T2D patients from the Local Swedish Diabetes registry.<h4>Results</h4>No association between the -168A-->G polymorphism in MHC2TA and MI was observed. However, in the Botnia cohort the AG/GG genotypes were associated with cardiovascular mortality after MI (1.78 [1.09-2.92], p = 0.02). In addition, the AG/GG genotypes were more common in subjects with MetS (40.1% vs. 36.9%, p = 0.03) and in non-diabetic subjects with microalbuminuria (45.4% vs. 36.5%, p = 0.003) compared to control subjects.<h4>Conclusions</h4>A polymorphism in MHC2TA was associated with cardiovascular mortality and predictors of cardiovascular mortality, microalbuminuria and MetS.
Project description:<h4>Background</h4>As the debate continues about whether obesity in metabolically healthy individuals is associated with poor outcomes or not, investigating the association between the obesity phenotypes and markers of subclinical myocardial injury will help identify those at risk for future cardiovascular events (cardiovascular disease [CVD]).<h4>Hypothesis</h4>We hypothesize that obesity phenotypes including metabolically healthy obesity (MHO) is associated with subclinical myocardial injury (SC-MI).<h4>Methods</h4>This analysis included 3423 participants (57.85?±?13.06?years, 53.3% women) without known CVD from National Health and Nutrition Examination Survey (NHANES) III. Multivariable logistic regression models were used to examine the cross-sectional association between four obesity phenotypes (metabolically healthy nonobese (MHNO) [reference], metabolically unhealthy nonobese (MUNO), MHO, and metabolically unhealthy obese (MUO) with SC-MI. SC-MI was defined from the 12-lead electrocardiogram as cardiac infarction/injury score???10 units. Metabolic syndrome (MetS) was defined according to the International Diabetes Federation consensus definition. Obesity was defined as body mass index ?30?kg/m<sup>2</sup> .<h4>Results</h4>MUO was associated with higher odds of SC-MI compared with MHNO (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.22-1.92, P?=?0.0005). This association was stronger in men vs women (OR [95% CI]: 2.20 [1.58-2.07] vs 1.08 [0.79-1.48]), respectively; interaction P-value?=?0.002) but was consistent in subgroups stratified by age and race. There was no significant association of MHO or MUNO with SC-MI compared with MHNO, but there was a trend toward higher odds of SC-MI in the MUNO group (P-value for trend across MHNO, MUNO, and MUO?=?0.0002).<h4>Conclusions</h4>Our findings suggest that a combination of obesity and MetS confers worse prognosis and early preventive strategies aimed at weight loss and management of MetS components may decrease the risk of future poor outcomes.
Project description:Metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors that include: abdominal obesity, dyslipidaemia, hypertension, insulin resistance and impaired glucose tolerance. Recent genome wide association studies have identified several susceptibility regions involved in lipid metabolism that are also associated with MetS. We have explored the association of 9 genetic polymorphisms involved in lipid metabolism and hypertension, including: MTHFR C677T, SELE L554F, FGB - 455G>A, GNB3 C825T, ZNF259 C>G, PSRC-1 A>G, CETP I405V, LPL S447X and LPA C>T in 97 subjects with MetS and 96 individuals without MetS who were recruited randomly from Mashhad stroke and heart atherosclerotic disorder (MASHAD) study using a stratified cluster random sampling technique. Anthropometric parameters and biochemical measurements were determined in all the subjects. Genotyping was carried out followed by univariate and multivariate analyses. The subjects with MetS had a higher triglyceride and lower HDL- C. CG+ GG genotypes of ZNF259 polymorphism (rs964184 C>G) and TT+CT genotypes of MTHFR C677T (rs1801133) were associated with MetS, and individuals carrying the G allele for ZNF259 or the T allele for MTHFR polymorphisms were associated with MetS (e.g, odds ratio (OR) for CG+GG genotypes vs. CC wild type: 2.52, CI=1.33-4.77; P=0.005). However, after multiple comparison adjustment, this relationship remained significant only for CG+ GG genotypes of ZNF259 polymorphism. Moreover, the ZNF259 CG+ GG genotypes were associated with increased serum concentrations of triglycerides and LDL-C, compared to the wild type. These data support the necessity for further studies in larger multicenter settings.
Project description:<h4>Objective</h4>To determine the association of TRIB3 Q84R polymorphism with metabolic syndrome (MetS) and carotid atherosclerosis.<h4>Research design and methods</h4>A case-control study enrolled 513 Chinese subjects in three groups: control, MetS, and obese. The functional TRIB3 Q84R polymorphism was genotyped among subjects undergoing carotid ultrasonography. The clinical and biochemical characteristics were determined.<h4>Results</h4>For individuals with the TRIB3 R84 allele, the odds ratio for developing MetS was 2.349 (P = 0.018), abdominal obesity 2.351 (P = 0.012), hypertriglyceridemia 2.314 (P = 0.00003), and insulin resistance 1.697 (P = 0.023). Likewise, the odds ratio for individuals with the TRIB3 R84 allele to develop thickened intima-media thickness was 2.208 (P = 0.040).<h4>Conclusions</h4>Individuals with the functional TRIB3 Q84R polymorphism are at risk for MetS. The TRIB3 R84 allele especially predisposes to carotid atherosclerosis in part through the effects of abdominal obesity, hypertriglyceridemia, and insulin resistance.
Project description:<h4>Background</h4>Previous studies have suggested that abnormal sleep duration is associated with increased risk of metabolic syndrome (MetS). However, evidence on the association of sleep duration with stroke, myocardial infarction (MI) and tumors in populations with MetS is limited.<h4>Methods</h4>A total of 8968 participants (2754 with MetS at baseline) were recruited in this retrospective study between March 2012 and December 2012. The baseline characteristics and information on sleep duration were collected by self-reported questionnaires. In addition, physical examination and blood test were also performed. The outcome events in this study were new onset of stroke, MI and tumors during subsequent follow-up. Multivariate logistic regressions were adopted to investigate the relationships between sleep duration and outcome events among different sleep duration groups (<?6?h, 6-7?h, 7-8?h [reference], 8-9?h, and?>?9?h per day) in participants with MetS.<h4>Results</h4>The mean self-reported total sleep duration was 7.8?±?1.2?h. Compared with participants with MetS slept for 7-8?h per day, the adjusted odds ratios (ORs) for those slept for >?9?h in stroke, MI and tumors were 2.014 (95% confidence interval [CI]: 1.184-3.426, P?=?0.010), 1.731 (95% CI: 0.896-3.344, P?=?0.102) and 2.159 (95% CI: 0.991-4.704, P?=?0.053), respectively, whereas the adjusted ORs for those slept for <?6?h in stroke, MI and tumors were 2.249 (95% CI: 0.973-5.195, P?=?0.058), 1.213 (95% CI, 0.358-4.104, P?=?0.756) and 1.743 (95% CI, 0.396-7.668, P?=?0.462), respectively.<h4>Conclusions</h4>Long sleep duration (>?9?h) significantly increased the risk of stroke but not MI and tumors in individuals with MetS compared with 7-8?h of sleep duration. Short sleep duration (<?6?h) was not associated with the increased risk of stroke, MI and tumors in individuals with MetS.
Project description:Metabolic syndrome (MetS) is a clustering of metabolic abnormalities that is associated with increased risk of developing cardiovascular disease and type 2 diabetes. There is growing body of data showing the associations of genetic variants of the genes involved in the PI3K/AKT/mTOR pathway with diabetes and obesity. We aimed to investigate the association between MetS and its components with the genetic polymorphism in AKT1, rs1130233 (T > C). Total of 618 participants, recruited from Mashhad stroke and heart atherosclerosis disorder cohort (MASHAD study). Patients with MetS were defined by using international diabetes federation (IDF) criteria (n = 326) and those without MetS (n = 261) were recruited. Anthropometric and biochemical parameters were measured in all subjects. Genetic analysis for the rs1130233 polymorphism was performed, using the ABI-StepOne instruments with SDS version-2.0 software. Individuals with MetS had a significantly higher levels of BMI, waist-circumference, total cholesterol, triglyceride, high sensitivity-c reactive protein (hs-CRP) and blood-pressure, and lower concentrations of high density lipoprotein (HDL-C), compared to non-MetS individuals (P < 0.05). The association between the rs1130233 and MetS was not significant. Subjects with a CC or CT genotypes had a significantly higher serum hs-CRP-level (OR: 1.5; 95% CI (1.05-2.1), P = 0.02). Additionally, subjects who carried the TC genotype had a higher BMI compared to the CC genotype (p value = 0.045). Our findings demonstrated that AKT1, rs1130233 (T > C) polymorphism was associated with major components of MetS such as hs-CRP, and BMI, indicating further investigation in a multi-center setting to explore its value as an emerging biomarker of risk stratification marker.
Project description:BACKGROUND/OBJECTIVES:The frequency of metabolic syndrome (MetS) is significantly higher in schizophrenia (SCH) patients, when compared to the general populatiotin. The goal of this study was to evaluate whether genetic variants T-786C (rs2070744), G894T (rs1799983) and C774T (rs1549758) in the endothelial nitric oxide (NOS3) gene and/or their haplotypes could be associated with the risk of MetS in SCH patients or healthy subjects from Russian population. SUBJECTS/METHODS:We performed two case-control comparisons. NOS3 polymorphisms were genotyped in 70 SCH patients with MetS, 190 normal weight SCH patients, 155 MetS patients, and 100 healthy controls. MetS was defined as per the criteria proposed by the International Diabetes Federation (IDF). Anthropometric, clinical, biochemical parameters, and serum nitrite concentrations were measured in all samples. Haplotype frequency estimations and linkage disequilibrium measures were made using Haploview 4.2. RESULTS:The higher C allele (P?=?0.009) and lower TT genotype (P?=?0.008) frequencies of T-786C polymorphism were found in SCH patients with MetS compared to those in normal weight SCH patients. SCH patients with MetS who were carriers of the T-786C TT genotype had lower serum total cholesterol levels in comparison to the CC genotype (P?=?0.016). Furthermore, the 774T/894T haplotype was more frequent in non-SCH individuals with MetS compared to healthy controls (P?=?0.0004, odds ratio?=?2.18, 95% confidence interval 1.4-3.37). Conversely, the most common haplotype 774C/894G was less frequent in MetS patients than in healthy controls (P?=?0.013, odds ratio?=?0.61, 95% confidence interval 0.41-0.9). CONCLUSIONS:These results indicate that the NOS3 T-786C promoter polymorphism was closely associated with MetS risk in SCH patients. In addition, the haplotypes composed of G894T and C774T polymorphisms are associated with the MetS susceptibility in Russian population.
Project description:BACKGROUND: Increased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors. METHODS: A total of 208 Thai subjects, aged 35-75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated. RESULTS: Arterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype. CONCLUSIONS: Our findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population.
Project description:AIM:To investigate if there is an association between M235T polymorphism of angiotensinogen gene and myocardial infarction (MI) risk and perform a meta-analysis and an in silico approach. METHODS:This case-control study included 340 participants (155 MI patients and 185 controls) examined at Kashan University of Medical Sciences (Kashan, Iran) between 2013 and 2015. Meta-analysis included 25 studies with 6334 MI patients and 6711 controls. Bioinformatics tools were applied to evaluate the impact of M235T polymorphism on angiotensinogen function and structure. RESULTS:Genetic association study revealed a significant association between TT genotype (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.08-4.00, P=0.029) and T allele (OR 1.45, 95% CI 1.06-1.99, P=0.021) and MI risk. Meta-analysis also revealed a significant association between M235T polymorphism and MI risk in allelic (OR 1.55, 95% CI 1.10-2.18, P=0.012) and recessive (OR 1.69, 95% CI 1.13-2.53, P=0.010) models within Asian population. In silico-analysis revealed that M235T fundamentally changed the function of angiotensinogen (score 32; expected accuracy 66%). CONCLUSIONS:Our study suggests that M235T polymorphism might be a helpful biomarker for screening of susceptible individuals for MI in Asian population.
Project description:Background:The relationships between apolipoprotein A-I (APOA-I), apolipoprotein B (APOB) with insulin resistance, metabolic syndrome (MetS) are unclear in OSA. We aimed to evaluate whether the multiple single nucleotide polymorphism (SNP) variants of APOA-I and APOB exert a collaborative effect on insulin resistance and MetS in OSA. Methods:Initially, 12 APOA-I SNPs and 30 APOB SNPs in 5259 subjects were examined. After strict screening, four APOA-I SNPs and five APOB SNPs in 4007 participants were included. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of APOA-I and APOB. Logistic regression analyses were used to evaluate the relationships between APOA-I/APOB genetic polymorphisms, insulin resistance, and MetS in OSA. Results:Serum APOB levels increased the risk of insulin resistance and MetS adjusting for age, gender and BMI [odds ratio (OR?=?3.168, P?<?0.001; OR?=?6.098, P?<?0.001, respectively]. APOA-I GRS decreased the risk of insulin resistance and MetS after adjustments (OR?=?0.917, P?=?0.001; OR?=?0.870, P?<?0.001, respectively). APOB GRS had no association with insulin resistance (OR?=?1.364, P?=?0.610), and had weak association with MetS after adjustments (OR?=?1.072, P?=?0.042). In addition, individuals in the top quintile of the APOA-I genetic score distribution had a lower risk of insulin resistance and MetS after adjustments (OR?=?0.761, P?=?0.007; OR?=?0.637, P?<?0.001, respectively). Conclusions:In patients with OSA, cumulative effects of APOA-I genetic variations decreased the risk of insulin resistance and MetS, whereas multiple APOB genetic variations had no associations with insulin resistance and weak association with MetS.