| 1. The association between CYBA polymorphisms and atherosclerosis in a Chinese population1.1Physical activity modifies the association between rs1049255, rs7195830polymorphisms and small artery elasticity in a Chinese populationEmerging evidence suggests that increased superoxide production is responsible for a significant proportion of endothelial dysfunction. The relationship between variants of the CYBA gene and cardiovascular diseases is currently debated. In present study, we determined to investigate the influence of CYBA polymorphisms (rs1049255and rs7195830) on arterial elasticity in a Chinese population. In the2178participants enrolled in GaoYou study, we measured large artery elasticity (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA polymorphisms and calculated the energy expenditure. The AA genotype of the rs1049255polymorphism was associated with lower C2than were the GG/AG genotypes (5.31±0.11vs.5.52±0.06ml/mmHg×100; P=0.01). Further analyses revealed an interaction between CYBA polymorphisms and physical activity with respect to C2(P=0.007for rs1049255, P=0.038for rs7195830). In less physically active participants, the AA genotype of the rs1049255polymorphism was associated with a significantly lower C2than the GG/AG genotypes (4.69±≈0.16vs.5.26±0.19ml/mmHg×100; P0.008). In physically active participants, the GG/AG genotype of rs7195830polymorphism was correlated with higher C2values compared to AA (5.84±0.08vs.5.08±0.32ml/mmHg×100; P=0.049). Haplotype analyses revealed higher C2values in rs1049255G-rs7195830G carriers (P=0.0015). In conclusion, the rs1049255and rs7195830polymorphisms of the CYBA gene were associated with C2in a Chinese population; physical activity could modify this genetic effect. 1.2Smoking habit modifies the association between C242T polymorphism and brachial-ankle pulse wave velocity in a Chinese populationGrowing evidence indicated that oxidative stress plays an important role in atherosclerosis. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase is the major source of superoxide production. The p22phox encoded by the CYBA gene could be the most essential component in the activation of NADPH oxidase. The C242T polymorphism (rs4673) is the most common among various variants on CYBA gene. Nowadays, there are many studies on the relationship between C242T polymorphism and diverse cardiovascular diseases, but the results are still conflicting. The aim of the present study is to explore the association between C242T polymorphism and brachial-ankle pulse wave velocity (baPWV) and demonstrated the modification effect of smoking habit. In the4373participants over an age range of18-74years enrolled in GaoYou study, we measured baPWV non-invasively, asked the individual smoking habit and genotyped the C242T polymorphism. In the entire population, after adjustment of age, sex, heart rate, antihypertensive medication, waist-to-hip ratio, body mass index, mean arterial pressure, total cholesterol, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, triglyceride level and serum glucose, no difference of baPWV was found between the CT+TT genotype and CC genotype (1480.7±9.1vs.1483.6±3.5cm/s, P=0.76). In futher analyses, interaction was found between C242T genotypes and smoking habit in relation to baPWV (P=0.033). In smokers, CT+TT genotype was associated with lower baPWV values compared to that of CC genotype (1517.5±14.4vs.1551.8±6.1cm/s, P=0.029) after adjustment for the same covariates, while in non-smokers, no such difference was found between genotypes (1463.7±11.6vs.1447.5±4.3cm/s, P=0.19). In conclusion, the C242T polymorphism of the CYBA gene was associated with baPWV in a Chinese population; smoking habit could modify this genetic effect. 2. Genetically elevated circulating levels of uric acid and brachial-ankle pulse wave velocity in a Chinese populationElevated circulating levels of uric acid and increased arterial stiffness are associated with cardiovascular diseases. Numerous studies have reported an association between circulating levels of uric acid and arterial stiffness. We employed the method of Mendelian randomization to test whether this association is causal. In the4387participants over an age range of18-74years enrolled in GaoYou study, we measured brachial-ankle pulse wave velocity (baPWV) non-invasively, tested the circulating levels of uric acid and genotyped the uric acid polymorphisms (rs2231142, rsl1722228and rs6855911). After adjusted for age, sex, diuretics medication, other antihypertensive medication, body mass index, waist-to-hip ratio and diabetic mellitus, there was a significant allelic difference in uric acid levels for each genotype (P<0.0001for rs2231142; P<0.0001for rs11722228; P=0.039for rs6855911), while such difference was disappeared when subjects with diuretics medication were removed for rs6855911polymorphism (P=0.077). BaPWV was significantly associated with circulating levels of uric acid after the adjustment for cardiovascular risk factors and other potential confounders (P<0.0001). However, neither the single polymorphism nor accumulation of culprit alleles was associated with baPWV (P=0.12for rs2231142; P=0.73for rs11722228; P for trend=0.67for combined analysis of culprit alleles). These results do not support a causal role of circulating levels of uric acid in the development of arterial stiffness. |
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