Cardiac autonomic dysfunction : effects from particulate air pollution and protection by dietary methyl nutrients and metabolic polymorphisms

Background - Particulate air pollution is associated with cardiovascular mortality and morbidity. To help identify mechanisms of action and protective/susceptibility factors, we evaluated whether the effect of particulate matter <2.5 mu m in aerodynamic diameter ( PM2.5) on heart rate variability was modified by dietary intakes of methyl nutrients ( folate, vitamins B-6 and B-12, methionine) and related gene polymorphisms ( C677T methylenetetrahydrofolate reductase [ MTHFR] and C1420T cytoplasmic serine hydroxymethyltransferase [ cSHMT]). Methods and Results - Heart rate variability and dietary data were obtained between 2000 and 2005 from 549 elderly men from the Normative Aging Study. In carriers of [ CT/TT] MTHFR genotypes, the SD of normal-to-normal intervals was 17.1% ( 95% CI, 6.5 to 26.4; P = 0.002) lower than in CC MTHFR subjects. In the same [ CT/TT] MTHFR subjects, each 10-mu g/m(3) increase in PM2.5 in the 48 hours before the examination was associated with a further 8.8% ( 95% CI, 0.2 to 16.7; P = 0.047) decrease in the SDNN. In [ CC] cSHMT carriers, PM2.5 was associated with an 11.8% ( 95% CI, 1.8 to 20.8; P = 0.02) decrease in SDNN. No PM2.5-SSDN association was found in subjects with either [ CC] MTHFR or [ CT/TT] cSHMT genotypes. The negative effects of PM2.5 were abrogated in subjects with higher intakes ( above median levels) of B-6, B-12, or methionine. PM2.5 was negatively associated with heart rate variability in subjects with lower intakes, but no PM2.5 effect was found in the higher intake groups. Conclusion - Genetic and nutritional variations in the methionine cycle affect heart rate variability either independently or by modifying the effects of PM2.5.