The association between atherosclerosis and plasma homocysteine concentration in the general population residing on remote islands in Japan

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Although hyperhomocysteinemia is an important and independent risk factor for vascular disease, the relationship between plasma homocysteine concentration (Hcy) and subclinical atherosclerosis in the general population remains controversial. We screened 1,845 participants who resided on Japanese remote islands and in mainland. Hcy and clinical values were measured, and methylenetetrahydrofolate reductase gene C677T polymorphism (C677T/MTHFR), which is an important genetic factor for regulating Hcy, was analyzed. Carotid intima-media thickness (CIMT) and the cardio ankle vascular index (CAVI) were measured to clinically evaluate subclinical atherosclerosis. CAVI had statistically significant association with Hcy (regression coefficient 0.3159, p=0.025), but CIMT was not. Hcy had statistically significant association with age, systolic blood pressure, high-density lipoprotein cholesterol, creatinine, C677T/MTHFR, smoking status and alcohol intake. Although C677T/MTHFR was not different among residing areas, Hcy was significantly higher on small islands than in other areas even after adjustment for confounding factors. We found the statistically significant association between Hcy and CAVI in the general population residing on Japanese remote islands, and significant differences in Hcy among residing areas, suggesting strong influence by acquired factors as well as genetic factors.