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Association Between MTHFR Gene Common Variants, Serum Homocysteine, and Risk of Early-Onset Coronary Artery Disease: A Case–Control Study

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Abstract

The common variants of the methylenetetrahydrofolate reductase (MTHFR) gene are related to the activity of the MTHFR enzyme and the concentrations of blood homocysteine (Hcy). This study was designed to investigate the associations of MTHFR in Chinese populations with early-onset coronary artery disease (EOCAD). The two common variants of the MTHFR gene were genotyped in 875 EOCAD patients and 956 controls using PCR, followed by direct sequencing of the PCR product. Serum levels of Hcy were measured using an automatic biochemistry analyzer. A significant association between the MTHFR-677C/T variant and the risk of EOCAD was detected in CC versus TT (odds ratio (OR) 1.456, 95% confidence interval (CI) 1.120–1.892), dominant genetic model (OR 1.266, 95% CI 1.027–1.546), and recessive genetic model (OR 1.306, 95% CI 1.040–1.639). Hcy was most abundant in TT genotype (18.31 ± 7.22 μmol/L), least abundant in CC genotype (11.37 ± 5.23 μmol/L), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 μmol/L). Elevated serum Hcy levels were an independent risk factor for EOCAD (ORadjust 1.431, 95% CI 1.135–1.763). Our findings indicated that the T allele of -677C/T MTHFR variant predisposes to high levels of Hcy, and that the T allele is an important risk factor for EOCAD in the Chinese population.

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Funding

The work was fully supported by grants from the National Natural Science Foundation of China (Grant No. 81672073), and China Postdoctoral Science Foundation (Grant No. 2016M590620).

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Authors and Affiliations

  1. Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China

    Shao-Yan Zhang, Chao Xuan, Jie Zhu, Kang Yue, Peng Zhao, Li-Min Lun & Qing-Wu Tian

  2. Department of Anesthesiology, Weishan People’s Hospital, Jining, China

    Xue-Chun Zhang

  3. Department of Surgery, TEDA International Cardiovascular Hospital, Tianjin & The Affiliated Hospital of Hangzhou Normal University and Zhejiang University, Hangzhou, China

    Guo-Wei He

  4. Department of Surgery, Oregon Health and Science University, Portland, OR, USA

    Guo-Wei He

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  1. Shao-Yan Zhang
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  2. Chao Xuan
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  3. Xue-Chun Zhang
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  4. Jie Zhu
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  5. Kang Yue
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Correspondence to Chao Xuan or Qing-Wu Tian.

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Zhang, SY., Xuan, C., Zhang, XC. et al. Association Between MTHFR Gene Common Variants, Serum Homocysteine, and Risk of Early-Onset Coronary Artery Disease: A Case–Control Study. Biochem Genet 58, 245–256 (2020). https://doi.org/10.1007/s10528-019-09937-x

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