Genetic polymorphisms of key enzymes in folate metabolism affect the efficacy of folate therapy in patients with hyperhomocysteinaemia

Du, Binghui; Tian, Huizi; Tian, Dean; Zhang, Chengda; Wang, Wenhua; Wang, Lianke; Ge, Mengying; Hou, Quanliang; Zhang, Weidong

doi:10.1017/s0007114518000508

Cited by 28 publications

(41 citation statements)

References 29 publications

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“…Therefore, in our study, we selected two GRS methods, SC-GRS and wGRS (DL-GRS), to analyse the efficacy on efficacy of folic acid treatment for HHcy. The direction of the six SNP affecting the efficacy of folic acid therapy was consistent with previous studies (17,18,(24)(25)(26)(27) . Especially, three SNP (rs1801131, rs1801133 and rs1801394) showed significant association with the folic acid efficacy.…”

Section: Discussionsupporting

confidence: 90%

“…The study involved 638 HHcy patients (Hcy ≥ 15 μmol/l). The detailed study design estimation had been described elsewhere (17) . We retrospectively analysed information on age, sex, smoking, alcohol consumption, disease history, biochemical indicators, genetic polymorphisms and so on.…”

Section: Study Participantsmentioning

confidence: 99%

“…As described previously, the therapy was effective if patients' Hcy levels decreased to 15 μmol/l or less, which put them in the success group. The therapy was unsuccessful if patients' Hcy levels were greater than or equal to 15 μmol/l, which put them in the failure group (17) . The study was approved by the Ethics Review Committee of the Life Science of Zhengzhou University.…”

Section: Study Participantsmentioning

confidence: 99%

“…We selected six previously identified SNP affecting the efficacy of folic acid therapy (17,18,(24)(25)(26)(27) . All these SNP had minor allele frequency > 0•05 in the Chinese population.…”

Section: Snp Selection and Genotypingmentioning

confidence: 99%

“…These may be caused by genetics. Some studies have shown that genetic polymorphisms of key enzymes in folic acid/Hcy metabolism not only affect the level of baseline Hcy, but also affect the efficacy of folic acid in reducing Hcy (17,18) . So far, studies on the efficacy of folic acid therapy have only explored the impacts of single nucleotide polymorphism (SNP), and there is a certain one-sidedness.…”

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confidence: 99%

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Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Zhang

Liu

et al. 2019

Br J Nutr

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No risk assessment tools for the efficacy of folic acid treatment for hyperhomocysteinaemia (HHcy) have been developed. We aimed to use two common genetic risk score (GRS) methods to construct prediction models for the efficacy of folic acid therapy on HHcy, and the best gene–environment prediction model was screened out. A prospective cohort study enrolling 638 HHcy patients was performed. We used a logistic regression model to estimate the associations of two GRS methods with the efficacy. Performances were compared using area under the receiver operating characteristic curve (AUC). The simple count genetic risk score (SC-GRS) and weighted genetic risk score (wGRS) were found to be independently associated with the efficacy of folic acid treatment for HHcy. Using the SC-GRS, per risk allele increased with a 1·46-fold increased failure risk (P < 0·001) after adjustment for traditional risk factors, including age, sex, BMI, smoking, alcohol consumption, history of diabetes, history of hypertension, history of hyperlipidaemia, history of stroke and history of CHD. When used the wGRS, the association was strengthened (OR = 2·08, P < 0·001). Addition of the SC-GRS and wGRS to the traditional risk model significantly improved the predictive ability by AUC (0·859). A precise gene–environment predictive model with good performance was developed for predicting the treatment failure rate of folic acid therapy for HHcy.

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Section: Discussionsupporting

confidence: 90%

Section: Study Participantsmentioning

confidence: 99%

Section: Study Participantsmentioning

confidence: 99%

Section: Snp Selection and Genotypingmentioning

confidence: 99%

mentioning

confidence: 99%

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Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Zhang

Liu

et al. 2019

Br J Nutr

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Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus

Xie

et al. 2019

Food Science & Nutrition

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Interest in the high folate status of pregnant women has increased due to its role in the prevention of neural tube defects (NTDs). The effect of increased red blood cell (RBC) folate status during the second trimester of pregnancy on gestational diabetes mellitus (GDM) remains unclear. We measured RBC folate concentrations by competitive protein‐binding assay and obtained clinical information from electronic medical records. Logistic regression analysis was used to explore the associations of RBC folate concentrations with risks of gestational diabetes mellitus (GDM). We further assessed the potential nonlinear relations between continuous log‐transformed RBC folate concentrations and GDM risk by using the restricted cubic splines. We observed high RBC folate concentrations in GDM patients compared to control group [median (interquartile range, IQR), GDM vs. controls: 1,554.03 (1,240.54–1,949.99) vs. 1,478.83 (1,124.60–1,865.71) nmol/L, p = .001]. Notably, high folate concentrations were significantly associated with an increased risk of GDM [RR per 1‐SD increase: 1.16 (1.03, 1.30), p = .012] after adjustment for maternal age, parity, and body mass index (BMI) at enrollment. In the restricted cubic spline model, a test of the null hypothesis of the linear relationship was rejected (p = .001). Our study firstly showed that maternal RBC folate concentrations during the second trimester of pregnancy increase the risk of GDM in a Chinese population. Further randomized clinical trials (RCTs) are warranted to confirm the adverse effect.

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Analysis of the frequency distribution of five single‐nucleotide polymorphisms of the MTRRgene in a Chinese pediatric population with acute lymphoblastic leukemia

Kong

Wang

2022

Pharmacotherapy

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Study Objective The objective of the present study was to examine the frequency distribution of five single‐nucleotide polymorphisms (SNPs; rs1801394 A>G, rs1532268 C>T, rs162036 A>G, rs10380 C>T, and rs9332 C>T) of the methionine synthase reductase (MTRR) gene, their effects on methotrexate (MTX) concentration, and the risk of relapse in a Chinese pediatric population with acute lymphoblastic leukemia (ALL). Design This was a retrospective single‐center study, and all analyses were exploratory. Setting Pediatric Department of Beijing Shijitan Hospital, Capital Medical University, Beijing, China. Patients One hundred and forty pediatric patients with ALL. Intervention All patients were treated according to the Chinese Children's Leukemia Group (CCLG)‐ALL 2008 protocol. Measurements and Main Results Serum MTX concentrations were measured using fluorescence polarization immunoassay. Genotyping of five SNPs was performed using the Sequenom MassARRAY iPLEX platform. Chinese children with ALL had a significantly lower frequency of rs1801394 G than European (EUR) and South Asian (SAS) populations; significantly lower frequency of rs1532268 T than American (AMR), EUR, and SAS populations; and significantly lower frequencies of rs162036 G, rs10380 T, and rs9332 T than African and AMR populations (p < 0.01). Seven haplotypes were observed, with the ACACC being the most common haplotype (49.9%) in our study. The median dose‐normalized concentrations of MTX in serum at 24 h in children with rs1532268 CT and TT genotypes were significantly higher than those with CC genotype (p = 0.04). Compared with children with AA‐CC‐AA‐CC‐CC diplotype, a significantly higher risk of relapse was observed in children with AG‐CC‐AA‐CC‐CC and AG‐CC‐AG‐CC‐CC diplotypes (p = 0.03 and 0.003, respectively). Conclusions The present study confirmed the ethnic differences in the distribution of MTRR rs1801394, rs1532268, rs162036, rs10380, and rs9332 polymorphisms. The rs1532268 polymorphism had greater effects on MTX disposition. The AG‐CC‐AA‐CC‐CC and AG‐CC‐AG‐CC‐CC diplotypes were significantly associated with higher risk of relapse of ALL.

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Genetic polymorphisms of key enzymes in folate metabolism affect the efficacy of folate therapy in patients with hyperhomocysteinaemia

Cited by 28 publications

References 29 publications

Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus

Analysis of the frequency distribution of five single‐nucleotide polymorphisms of the MTRRgene in a Chinese pediatric population with acute lymphoblastic leukemia

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