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Disease Markers
Volume 30 (2011), Issue 6, Pages 291-298
http://dx.doi.org/10.3233/DMA-2011-0787

Effects of Six Functional SNPs on the Urinary 8-Isoprostane Level in a General Japanese Population; Shimane COHRE Study

Yoji Suyama,1 Chikashi Matsuda,1 Minoru Isomura,2 Tsuyoshi Hamano,6 Kenji Karino,2 Masayuki Yamasaki,3 Shuhei Yamaguchi,4,6 Kuninori Shiwaku,4,6 Junichi Masuda,1,6 and Toru Nabika5,6

1Department of Laboratory Medicine, Shimane University School of Medicine, Izumo, Japan
2Department of Community Medicine Management, Shimane University School of Medicine, Izumo, Japan
3Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Izumo, Japan
4The Third Department of Internal Medicine, Shimane University School of Medicine, Izumo, Japan
5Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan
6The Center of Health Research and Education (COHRE), Shimane University, Izumo, Japan
7Department of Cancer Genomics, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan

Received 28 June 2011; Accepted 28 June 2011

Copyright © 2011 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oxidative stress is an important risk factor for cardiovascular diseases. Although a variety of genetic factors are assumed to contribute to the regulation of oxidative stress, evidence in human populations is insufficient. In this study, we therefore evaluated the effects of six functional single-nucleotide polymorphisms (SNPs) on the oxidative stress under a cross-sectional study design. Participants of the health examination in two neighboring counties were recruited in a mountainous region of Shimane prefeture, Japan (n = 1092). As a marker for the oxidative stress, the urinary 8-isoprostane (IsoP) was measured by ELISA. The six SNPs were genotyped using the Taqman method. None of the SNPs showed a significant effect on the IsoP level. However, the Generalized Multiple Dimensionality Reduction (GMDR) method identified that the combination of the two SNPs, MTHFR C677T and eNOS T-786C, showed a significant effect on the IsoP level in this population. The linear regression analysis confirmed that the high risk genotype identified in the GMDR was an independent factor influencing the IsoP even after adjustment of confounding factors. This result suggested that GMDR analysis might be useful to identify concealed effects of combined SNPs.