A Potential Strategy for Atherosclerosis Prevention in Modernizing China - Hyperhomocysteinemia, MTHFR C677T Polymorphism and Air Pollution (PM2.5) on Atherogenesis in Chinese Adults.

ABSTRACT

BACKGROUND: Atherosclerosis is one of the most important global health hazards and air pollution (AP, PM2.5) has been implicated. In addition to traditional risk factors hyperhomocysteinemia (HC) has been recognized in many parts of China related to risk of stroke. METHODS: To evaluate the impact of HC (homocysteine >14µmol/l) and PM2.5 air pollution on atherogenesis in modernizing China, we studied 756 asymptomatic Chinese in China from 1998-2007. PM2.5 exposure, HC, folate, and methylenetetrahydrofolate reductase (MTHFR) C/T genotype were evaluated. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. Locations were categorized as zones 1, 2 and 3, with increasing PM2.5 exposure. RESULTS: HC was higher (19.4±13.1 and 27.1±25.1µmol/l) in high PM2.5-polluted zones 2 and 3 than in zone 1 (9.7±4.5µmol/l, p<0.0015). The top HC tertile was characterized by lower folate and vitamin B12, but a higher proportion of the MTHFR TT genotype, Metabolic Syndrome (MS) and PM2.5 level (p=0.0018). FMD was significantly lower (7.3±2.3%) and carotid IMT thicker (0.63±0.12mm) in the top HC tertile, compared with low HC tertile (8.4±2.5%, p<0.0001; 0.57±0.1mm, p<0.0001 respectively). Similar differences in FMD and IMT were seen in zones 2 and 3, compared with zone 1 (p<0.0001). On multivariate regression, HC was related to male gender (beta=0.106, p=0.021), MTHFR-TT (beta=0.935, p<0.0001), locations (beta=0.230, p<0.0001) and folate-MTHFR interaction (beta=-0.566, p<0.0001). FMD was related to age (beta= -0.221; p<0.0001), male gender (beta= -0.194, p=0.001) PM2.5 and location (beta=-0.285 to -0.303, p<0.0001). Carotid IMT was related to PM2.5 (beta=0.173, p<0.0001), HC (0.122, p=0.006) but not to MTHFR or location, independent of age, gender, MS, and LDL-C. No significant HC-PM2.5 interaction effect on FMD and IMT was observed. CONCLUSION: HC and PM2.5 pollution but not MTHFR genotype were both related to carotid IMT, independent of other traditional risk factors. This has potential implications in dietary and AP strategies for atherosclerosis prevention in China.