Dankang Li1, Qinglin Zhao1, Xiaowen Huang1, Chengda Zhang2, Opolot Godfrey1, Weidong Zhang3. 1. Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. 2. Department of International Medicine, Beaumont Health System, Royal Oak, MI, 48073, USA. 3. Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. imooni@163.com.
Abstract
BACKGROUND: Folate supplementation treatment is the first-line therapy in hyperhomocysteinaemia (HHcy). Up to 40% of HHcy patients do not benefit from folate therapy. Genetic and epigenetic factors of one-carbon metabolism (1-CM) might be identified as a predictor of folate supplementation treatment response. In the present study, we attempt to identify whether genetic and epigenetic factors might predict folate treatment response. METHODS: A total of 230 patients with HHcy were involved in this prospective cohort study. Differences between baseline concentrations and concentrations obtained at 90 days of treatment were calculated to evaluate the treatment response. General linear models and Pearson correlation was used to explore associations among single-nucleotide polymorphisms (SNPs), DNA methylation, and folate treatment response. Finally, mediation analysis was performed to investigate whether DNA methylation of MTRR mediates the association between SNPs and treatment response. RESULTS: MTHFD rs1950902 and MTRR rs162036, rs1801394 was associated with the folate treatment response (P = 0.000, 0.048, and 0.043, respectively). CBS and CBS_2 DNA methylation was significantly associated with folate treatment response (P = 0.0009 and < 0.001). DNA methylation of MTHFR, MTR, and MTRR was also significantly associated with folate treatment response (P < 0.001). DNA methylation of MTRR and MTRR_1 mediated 40.71% and 40.47% of the effect of rs1801394 on folate treatment response, respectively. CONCLUSIONS: Our results indicated that the 1-CM gene SNPs and DNA methylation was associated with folate treatment response and can be further evaluated relationship between SNPs and DNA methylation in 1-CM with treatment response in a larger sample.
BACKGROUND:Folate supplementation treatment is the first-line therapy in hyperhomocysteinaemia (HHcy). Up to 40% of HHcy patients do not benefit from folate therapy. Genetic and epigenetic factors of one-carbon metabolism (1-CM) might be identified as a predictor of folate supplementation treatment response. In the present study, we attempt to identify whether genetic and epigenetic factors might predict folate treatment response. METHODS: A total of 230 patients with HHcy were involved in this prospective cohort study. Differences between baseline concentrations and concentrations obtained at 90 days of treatment were calculated to evaluate the treatment response. General linear models and Pearson correlation was used to explore associations among single-nucleotide polymorphisms (SNPs), DNA methylation, and folate treatment response. Finally, mediation analysis was performed to investigate whether DNA methylation of MTRR mediates the association between SNPs and treatment response. RESULTS: MTHFD rs1950902 and MTRRrs162036, rs1801394 was associated with the folate treatment response (P = 0.000, 0.048, and 0.043, respectively). CBS and CBS_2 DNA methylation was significantly associated with folate treatment response (P = 0.0009 and < 0.001). DNA methylation of MTHFR, MTR, and MTRR was also significantly associated with folate treatment response (P < 0.001). DNA methylation of MTRR and MTRR_1 mediated 40.71% and 40.47% of the effect of rs1801394 on folate treatment response, respectively. CONCLUSIONS: Our results indicated that the 1-CM gene SNPs and DNA methylation was associated with folate treatment response and can be further evaluated relationship between SNPs and DNA methylation in 1-CM with treatment response in a larger sample.
Authors: Yong Li; Jun Cheng; Wen-li Zhu; Jing-jing Dao; Li-ying Yan; Meng-yi Li; Shu-qin Li Journal: Beijing Da Xue Xue Bao Yi Xue Ban Date: 2005-02-18