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eNOS genotype modifies the effect of leisure-time physical activity on serum triglyceride levels in a Japanese population

Takahiro Higashibata1*, Nobuyuki Hamajima1, Mariko Naito1, Sayo Kawai1, Guang Yin1, Sadao Suzuki2, Yoshikuni Kita3, Hideshi Niimura4, Takeshi Imaizumi5, Keizo Ohnaka6, Kokichi Arisawa7, Masako Shigeta8, Hidemi Ito9, Haruo Mikami10, Michiaki Kubo11, Hideo Tanaka9 and Kenji Wakai1

Author Affiliations

1 Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

2 Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

3 Department of Health Science, Shiga University of Medical Science, Otsu, 520-2192, Japan

4 Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, Japan

5 Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, 849-8501, Japan

6 Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

7 Department of Preventive Medicine, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, 770-8503, Japan

8 Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan

9 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, 464–8681, Japan

10 Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, Chiba, 260-8717, Japan

11 Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, 230-0045, Japan

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Lipids in Health and Disease 2012, 11:150  doi:10.1186/1476-511X-11-150

Published: 5 November 2012



Nitric oxide is a key molecule not only in the cardiovascular system, but also in the metabolic-endocrine system. The purpose of this study was to examine possible associations of the NOS3 T-786C polymorphism (rs2070744) with serum lipid levels on the basis of lifestyle factors for tailoring prevention of dyslipidemia.


For this cross-sectional study, a total of 2226 subjects aged 35 to 69 years (1084 men and 1142 women) were selected from Japanese participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were recruited in eight areas throughout Japan between February 2004 and November 2008.


In a stratified analysis by leisure-time physical activity, the likelihood of hypertriglyceridemia (serum triglyceride levels ≥ 150 mg/dL) among subjects with the C allele was significantly lower than those without it in the active group (OR = 0.43, 95% CI = 0.22-0.84 in the fasting group), but not in the sedentary group. A gene-environment interaction between the T-786C polymorphism and leisure-time physical activity for hypertriglyceridemia was significant (P = 0.007 in the fasting group). Additionally, serum triglyceride levels (mean ± SD) across leisure-time physical activity classes decreased significantly only in the TC + CC genotype group (111 ± 60 mg/dL for sedentary, 95 ± 48 mg/dL for moderately active, 88 ± 44 mg/dL for very active, P for trend = 0.008 in the fasting group), but not in the TT genotype group. Total cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol levels had no significant association with the polymorphism.


This study suggests that the NOS3 T-786C polymorphism modifies the effect of leisure-time physical activity on serum triglyceride levels.

Cross-sectional study; Gene-environment interaction; Hypertriglyceridemia; Lifestyle-related disease; NOS3; Tailoring prevention