Abstract
Coronary atherosclerosis is a complex and progressive condition that involves many biological pathways, including the oxidative stress and inflammatory response pathways. To investigate the association between common genetic variation within these two pathways and coronary atherosclerosis, we performed a comprehensive two-stage candidate gene association study in a Chinese Han population. In stage I, 936 tag single-nucleotide polymorphisms (SNPs) within 116 candidate genes were genotyped in 293 coronary atherosclerosis cases and 293 age- and gender-matched healthy controls. In stage II, 51 SNPs from stage I were selected and further genotyped in an additional 1030 cases and 764 controls. In allele- and genotype-based association tests of stage II and a meta-analysis across the two stages, we identified three SNPs within three genes significantly associated with the disease, namely rs3212556 in ITGA2 (PCMH=9.20 × 10−5), rs854563 in PON1 (PCMH=1.92 × 10−4) and rs9283851 in THBS2 (PCMH=3.00 × 10−3). Haplotype analysis provided further supporting evidence for the association of rs3212556 (Pglobal<10−4) and rs854563 (Pglobal<10−4). Our study has identified three SNPs within ITGA2, PON1 and THBS2 that are associated with coronary atherosclerosis.
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Acknowledgements
We are most grateful to all the individuals who participated in this study and the collaborating clinics and physicians for referring individuals to the study. We thank Professor Momiao Xiong of Human Genetics Center, The University of Texas Health Science Center (Houston, TX, USA) for his encouraging discussion, Professor Aijun Sun of the Department of Cardiology, Zhongshan Hospital, Fudan University for their cooperation in collecting blood samples. The work was supported by the grants from Chinese High-Tech Program (2006AA020706, 2006AA02A406), Chinese National Natural Science Fund for Distinguished Young Scholars (30625019) and Shanghai Science and Technology Committee (09DZ2291900).
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Wang, Y., Fu, W., Xie, F. et al. Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population. J Hum Genet 55, 490–494 (2010). https://doi.org/10.1038/jhg.2010.53
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DOI: https://doi.org/10.1038/jhg.2010.53
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