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Serum folate mediates the associations of MTHFR rs1801133 polymorphism with blood glucose levels and gestational diabetes mellitus in Chinese Han pregnant women

Published online by Cambridge University Press:  09 February 2023

Yunguo Wang ,
Yiyun Wang ,
Yao Sun ,
Naijian Zhang ,
Xiaoshan Liang ,
Suhui Luo Open the ORCID record for Suhui Luo [Opens in a new window] ,
Lirong Dai ,
Chao Sun ,
Yungui Yang  and
Shuying Li
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Yunguo Wang
Affiliation:
Department of Orthopedics Surgery, Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin 300211, People’s Republic of China
Yiyun Wang
Affiliation:
Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
Yao Sun
Affiliation:
Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
Naijian Zhang
Affiliation:
Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
Xiaoshan Liang
Affiliation:
Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
Suhui Luo
Affiliation:
Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
Lirong Dai
Affiliation:
Community Health Service Center of Yangliuqing Town, Tianjin 300380, People’s Republic of China
Chao Sun
Affiliation:
Community Health Service Center of Yangliuqing Town, Tianjin 300380, People’s Republic of China
Yungui Yang
Affiliation:
Community Health Service Center of Zhangjiawo Town, Tianjin 300393, People’s Republic of China
Shuying Li
Affiliation:
Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin 300380, People’s Republic of China
Xumei Zhang
Affiliation:
Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
Qiang Zhang*
Affiliation:
Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin 300070, People’s Republic of China
*
*Corresponding author: Qiang Zhang, email qiangzhang@tmu.edu.cn
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Abstract

This study aimed to explore the mediation effects of one-carbon metabolism (OCM) related nutrients on the association between MTHFR rs1801133 polymorphism and gestational diabetes mellitus (GDM). Folate, vitamin B12 and homocysteine (Hcy) were measured in the serum of 1254 pregnant women. Linear and logistic regressions were used to estimate the associations of OCM nutrients and MTHFR rs1801133 polymorphism with blood glucose levels and GDM risk. Mediation analysis was applied to test the mediation effects of folate, vitamin B12 and Hcy on the association of MTHFR rs1801133 polymorphism with blood glucose concentrations and GDM. Pregnant women with MTHFR rs1801133 CC genotype had higher serum folate (10·75 v. 8·90 and 9·40 ng/ml) and lower serum Hcy (4·84 v. 4·93 and 5·20 μmol/l) than those with CT and TT genotypes. Folate concentrations were positively associated with fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG), 2-h plasma glucose (2-h PG) and GDM risk. Vitamin B12 levels were negatively correlated with FPG and GDM. Although no direct association was found between MTHFR rs1801133 genotypes and GDM, there were significant indirect effects of MTHFR rs1801133 CC genotype on FPG (β: 0·005; 95 % CI: 0·001, 0·013), 1-h PG (β: 0·006; 95 % CI: 0·001, 0·014), 2-h PG (β: 0·007; 95 % CI: 0·001, 0·015) and GDM (β: 0·006; 95 % CI: 0·001, 0·014) via folate. In conclusion, serum folate mediates the effect of MTHFR rs1801133 on blood glucose levels and GDM. Our findings potentially provide a feasible GDM prevention strategy via individualised folate supplementation according to the MTHFR genotypes.

Keywords

Gestational diabetes mellitusMTHFRFolateMediation effect
Type
Research Article
Information
British Journal of Nutrition , Volume 130 , Issue 8 , 28 October 2023 , pp. 1329 - 1337
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Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

†

These authors contributed equally to this work and they shared co-first authorship.

References

Wang, H, Li, N, Chivese, T, et al. (2022) IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group’s Criteria. Diabetes Res Clin Pract 183, 109050.10.1016/j.diabres.2021.109050CrossRefGoogle ScholarPubMed
McIntyre, HD, Catalano, P, Zhang, C, et al. (2019) Gestational diabetes mellitus. Nat Rev Dis Primers 5, 47.CrossRefGoogle ScholarPubMed
Lai, JS, Pang, WW, Cai, S, et al. (2018) High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus. Clin Nutr 37, 940–947.10.1016/j.clnu.2017.03.022CrossRefGoogle ScholarPubMed
Li, S, Hou, Y, Yan, X, et al. (2019) Joint effects of folate and vitamin B12 imbalance with maternal characteristics on gestational diabetes mellitus. J Diabetes 11, 744–751.10.1111/1753-0407.12899CrossRefGoogle ScholarPubMed
Saravanan, P, Sukumar, N, Adaikalakoteswari, A, et al. (2021) Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study). Diabetologia 64, 2170–2182.CrossRefGoogle ScholarPubMed
Chen, X, Zhang, Y, Chen, H, et al. (2021) Association of maternal folate and vitamin B12 in early pregnancy with gestational diabetes mellitus: a prospective cohort study. Diabetes Care 44, 217–223.10.2337/dc20-1607CrossRefGoogle ScholarPubMed
Li, S, Tian, X, Wang, Y, et al. (2022) Associations of maternal rs1801131 genotype in MTHFR and serum folate and vitamin B12 with gestational diabetes mellitus in Chinese pregnant women. Nutrients 14, 1169.10.3390/nu14061169CrossRefGoogle ScholarPubMed
Zhu, B, Ge, X, Huang, K, et al. (2016) Folic acid supplement intake in early pregnancy increases risk of gestational diabetes mellitus: evidence from a prospective cohort study. Diabetes Care 39, e36–e37.10.2337/dc15-2389CrossRefGoogle ScholarPubMed
Li, Q, Zhang, Y, Huang, L, et al. (2019) High-dose folic acid supplement use from prepregnancy through midpregnancy is associated with increased risk of gestational diabetes mellitus: a prospective cohort study. Diabetes Care 42, e113–e115.10.2337/dc18-2572CrossRefGoogle ScholarPubMed
Zheng, Y, Deng, H-Y, Qiao, Z-Y, et al. (2021) Homocysteine level and gestational diabetes mellitus: a systematic review and meta-analysis. Gynecol Endocrinol 37, 1–8.CrossRefGoogle ScholarPubMed
Clare, CE, Brassington, AH, Kwong, WY, et al. (2019) One-carbon metabolism: linking nutritional biochemistry to epigenetic programming of long-term development. Annu Rev Anim Biosci 7, 263–287.10.1146/annurev-animal-020518-115206CrossRefGoogle ScholarPubMed
Hiraoka, M & Kagawa, Y (2017) Genetic polymorphisms and folate status. Congenit Anom 57, 142–149.10.1111/cga.12232CrossRefGoogle ScholarPubMed
Khan, IA, Shaik, NA, Kamineni, V, et al. (2015) Evaluation of gestational diabetes mellitus risk in south Indian women based on MTHFR (C677T) and FVL (G1691A) mutations. Front Pediatr 3, 34.10.3389/fped.2015.00034CrossRefGoogle ScholarPubMed
Liu, PJ, Liu, Y, Ma, L, et al. (2020) Associations between gestational diabetes mellitus risk and folate status in early pregnancy and MTHFR C677T polymorphisms in Chinese women. Diabetes Metab Syndr Obes 13, 1499–1507.CrossRefGoogle ScholarPubMed
Shane, B, Pangilinan, F, Mills, JL, et al. (2018) The 677C→T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population. Am J Clin Nutr 108, 1334–1341.10.1093/ajcn/nqy209CrossRefGoogle Scholar
Jin, H, Cheng, H, Chen, W, et al. (2018) An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis. Am J Clin Nutr 107, 817–825.10.1093/ajcn/nqy035CrossRefGoogle ScholarPubMed
MacKinnon, DP, Fairchild, AJ & Fritz, MS (2007) Mediation analysis. Annu Rev Psychol 58:593–614.CrossRefGoogle ScholarPubMed
Zhang, Q, Zhang, X, Li, S, et al. (2021) Joint effect of urinary arsenic species and serum one-carbon metabolism nutrients on gestational diabetes mellitus: a cross-sectional study of Chinese pregnant women. Environ Int 156, 106741.10.1016/j.envint.2021.106741CrossRefGoogle ScholarPubMed
Chen, K, Zhou, Y-X, Li, K, et al. (2016) A novel three-round multiplex PCR for SNP genotyping with next generation sequencing. Anal Bioanal Chem 408, 4371–4377.10.1007/s00216-016-9536-6CrossRefGoogle ScholarPubMed
Baron, RM & Kenny, DA (1986) The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51, 1173–1182.10.1037/0022-3514.51.6.1173CrossRefGoogle ScholarPubMed
Thuesen, BH, Husemoen, LLN, Ovesen, L, et al. (2010) Lifestyle and genetic determinants of folate and vitamin B12 levels in a general adult population. Br J Nutr 103, 1195–1204.CrossRefGoogle Scholar
Tsang, BL, Devine, OJ, Cordero, AM, et al. (2015) Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies. Am J Clin Nutr 101, 1286–1294.10.3945/ajcn.114.099994CrossRefGoogle ScholarPubMed
Yang, B, Liu, Y, Li, Y, et al. (2013) Geographical distribution of MTHFR C677T, A1298C and MTRR A66G gene polymorphisms in China: findings from 15357 adults of Han nationality. PLoS One 8, e57917.CrossRefGoogle Scholar
Surendran, S, Adaikalakoteswari, A, Saravanan, P, et al. (2018) An update on vitamin B12-related gene polymorphisms and B12 status. Genes Nutr 13, 2.10.1186/s12263-018-0591-9CrossRefGoogle ScholarPubMed
Al-Batayneh, KM, Zoubi, MSA, Shehab, M, et al. (2018) Association between MTHFR 677C > T polymorphism and vitamin B12 deficiency: a case-control study. J Med Biochem 37, 141–147.10.1515/jomb-2017-0051CrossRefGoogle ScholarPubMed
Shiran, A, Remer, E, Asmer, I, et al. (2015) Association of vitamin B12 deficiency with homozygosity of the TT MTHFR C677T genotype, hyperhomocysteinemia, and endothelial cell dysfunction. Isr Med Assoc J 17, 288–292.Google Scholar
Radzicka, S, Ziolkowska, K, Zaborowski, MP, et al. (2019) Serum homocysteine and vitamin B12 levels in women with gestational diabetes mellitus. Ginekol Pol 90, 381–387.CrossRefGoogle ScholarPubMed
Dias, S, Adam, S, Rheeder, P, et al. (2021) No association between ADIPOQ or MTHFR polymorphisms and gestational diabetes mellitus in South African women. Diabetes Metab Syndr Obes 14, 791–800.CrossRefGoogle ScholarPubMed
Jankovic-Karasoulos, T, Furness, DL, Leemaqz, SY, et al. (2020) Maternal folate, one-carbon metabolism and pregnancy outcomes. Matern Child Nutr 17, e13064.10.1111/mcn.13064CrossRefGoogle ScholarPubMed
Preacher, KJ (2015) Advances in mediation analysis: a survey and synthesis of new developments. Annu Rev Psychol 66, 825–852.10.1146/annurev-psych-010814-015258CrossRefGoogle ScholarPubMed
Lee, H, Cashin, AG, Lamb, SE, et al. (2021) A guideline for reporting mediation analyses of randomized trials and observational studies: the AGReMA statement. JAMA 326, 1045–1056.CrossRefGoogle ScholarPubMed
Xu, M, Lv, X, Xie, L, et al. (2016) Discrete associations of the GCKR variant with metabolic risk in a Chinese population: longitudinal change analysis. Diabetologia 59, 307–315.10.1007/s00125-015-3788-0CrossRefGoogle Scholar
Guerra-García, MT, Moreno-Macías, H, Ochoa-Guzmán, A, et al. (2021) The -514C > T polymorphism in the LIPC gene modifies type 2 diabetes risk through modulation of HDL-cholesterol levels in Mexicans. J Endocrinol Invest 44, 557–565.10.1007/s40618-020-01346-xCrossRefGoogle ScholarPubMed
Maher, A & Sobczyńska-Malefora, A (2021) The relationship between folate, vitamin B12 and gestational diabetes mellitus with proposed mechanisms and foetal implications. J Fam Reprod Health 15, 141–149.Google ScholarPubMed
Pannia, E, Hammoud, R, Simonian, R, et al. (2020) [6S]-5-methyltetrahydrofolic acid and folic acid pregnancy diets differentially program metabolic phenotype and hypothalamic gene expression of wistar rat dams post-birth. Nutrients 13, E48.CrossRefGoogle ScholarPubMed
Pannia, E, Hammoud, R, Kubant, R, et al. (2021) High intakes of [6S]-5-methyltetrahydrofolic acid compared with folic acid during pregnancy programs central and peripheral mechanisms favouring increased food intake and body weight of mature female offspring. Nutrients 13, 1477.CrossRefGoogle ScholarPubMed
Yan, J, Zheng, YZ, Cao, LJ, et al. (2017) Periconceptional folic acid supplementation in Chinese women: a cross-sectional study. Biomed Environ Sci 30, 737–748.Google ScholarPubMed
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