Serum Folate and Vitamin B <sub>12</sub> Modify the Associations of <i>N6AMT1</i> Genetic Variants with Gestational Diabetes Mellitus: A Cross-Sectional Study in Chinese Pregnant Women

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Abstract

Purpose

This study aimed to explore the association between N-6 adenine-specific DNA methyltransferase 1 ( N6AMT1) single nucleotide polymorphisms (SNPs) and gestational diabetes mellitus (GDM) and the modification of the relationship by folate and vitamin B ₁₂.

Methods

A cross-sectional study involving 1303 pregnant women (262 GDM and 1041 non-GDM) was performed in Tianjin, China. Nine SNPs in N6AMT1 were genotyped, and serum folate, vitamin B ₁₂, and homocysteine (Hcy) levels were measured. The logistic regression models determined the odds ratios (ORs) for SNPs in N6AMT1 and the gene-nutrition interactions on GDM.

Results

N6AMT1 rs7282280, rs1048546, and rs1997605 were related to GDM under the dominant model after adjusting for multiple covariates. Individuals carrying the N6AMT1 rs7282280 TC/TT genotypes had a lower risk of developing GDM, regardless of serum folate and vitamin B ₁₂ levels. However, rs1048546 TG/GG genotypes were associated with lower GDM risk when serum folate ≥ 6.0 ng/mL. Pregnancies with the risk genotypes in N6AMT1 and higher serum folate or lower vitamin B ₁₂ are more prone to GDM. The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B ₁₂ (RERI: 2.54; 95% CI: 0.17, 4.92).

Conclusion

SNPs in N6AMT1 were found to be associated with GDM, and serum folate and vitamin B ₁₂ levels can modify their associations.

Related collections

Most cited references 41

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One-Carbon Metabolism in Health and Disease.

Gregory S Ducker, Joshua D Rabinowitz (2017)

One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention.

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Gestational diabetes mellitus

H McIntyre, Patrick Catalano, Cuilin Zhang … (2019)

Hyperglycaemia that develops during pregnancy and resolves after birth has been recognized for over 50 years, but uniform worldwide consensus is lacking about threshold hyperglycaemic levels that merit a diagnosis of 'gestational diabetes mellitus' (GDM) and thus treatment during pregnancy. GDM is currently the most common medical complication of pregnancy, and prevalence of undiagnosed hyperglycaemia and even overt diabetes in young women is increasing. Maternal overweight and obesity, later age at childbearing, previous history of GDM, family history of type 2 diabetes mellitus and ethnicity are major GDM risk factors. Diagnosis is usually performed using an oral glucose tolerance test (OGTT), although a non-fasting, glucose challenge test (GCT) is used in some parts of the world to screen women for those requiring a full OGTT. Dietary modification and increased physical activity are the primary treatments for GDM, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved. Oral hypoglycaemic agents, principally metformin and glibenclamide (glyburide), are also used in some countries. Treatment improves immediate pregnancy outcomes, reducing excess fetal growth and adiposity and pregnancy-related hypertensive disorders. GDM increases the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease, in both the mother and infant. Optimal management of mother and infant during long-term follow-up remains challenging, with very limited implementation of preventive strategies in most parts of the world.

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Prevalence of gestational diabetes mellitus in mainland China: A systematic review and meta‐analysis

Chenghan Gao, Xin Sun, Li Lu … (2018)

Abstract Aims/Introduction Pregnant women with gestational diabetes mellitus (GDM) are at a higher risk of adverse pregnancy outcomes. The aim of the present study was to estimate the pooled prevalence of GDM in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria. Materials and Methods We carried out a systematic review by searching both English and Chinese literature databases. Random effects models were used to summarize the prevalence of GDM in mainland China. Subgroup and sensitivity analyses were carried out to address heterogeneity. Publication bias was evaluated using Egger's test. Results A total of 25 papers were included in the meta‐analysis, involving 79,064 Chinese participants. The total incidence of GDM in mainland China was 14.8% (95% confidence interval 12.8–16.7%). Subgroup analysis showed that the age, bodyweight and family history of diabetes mellitus could significantly increase the incidence of GDM. Conclusions To the best of our knowledge, this systematic review is the first to estimate the pooled prevalence of GDM among women in mainland China according to International Association of Diabetes and Pregnancy Study Groups criteria. The results of our systematic review suggest a high prevalence of GDM in mainland China, indicating that this country might have the largest number of GDM patients worldwide.

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Author and article information

Journal

Journal ID (nlm-ta): Diabetes Metab Syndr Obes

Journal ID (iso-abbrev): Diabetes Metab Syndr Obes

Journal ID (publisher-id): dmso

Title: Diabetes, Metabolic Syndrome and Obesity

Publisher: Dove

ISSN (Electronic): 1178-7007

Publication date (Electronic): 17 April 2024

Publication date Collection: 2024

Volume: 17

Pages: 1781-1791

Affiliations

[1 ]Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University , Tianjin, People’s Republic of China

[2 ]Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University , Tianjin, People’s Republic of China

[3 ]Department of Endocrinology, Tianjin Xiqing Hospital , Tianjin, People’s Republic of China

[4 ]Department of Obstetrics and Gynecology, Tianjin Xiqing Hospital , Tianjin, People’s Republic of China

[5 ]Department of Obstetrics and Gynecology, Women’s and Children’s Health Center of Dongchangfu District , Liaocheng, People’s Republic of China

[6 ]Department of Reproductive Health, Women’s and Children’s Health Center of Dongchangfu District , Liaocheng, People’s Republic of China

[7 ]Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University , Tianjin, People’s Republic of China

[8 ]Department of Biomedical Information and Library, Tianjin Medical University , Tianjin, People’s Republic of China

[9 ]NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University , Tianjin, People’s Republic of China

Author notes

Correspondence: Shuying Li, Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, 300380, People’s Republic of China, Email lsy_tj2006@163.com

Qiang Zhang, Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, People’s Republic of China, Tel +86 022 83336633, Email qiangzhang@tmu.edu.cn

[*]

These authors contributed equally to this work

Author information

Qiang Zhang http://orcid.org/0000-0002-8359-3715

Article

Publisher ID: 451045

DOI: 10.2147/DMSO.S451045

PMC ID: 11032668

PubMed ID: 38645658

SO-VID: bd4c1434-8996-4d18-8a00-928bdb1dd45d

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 05 January 2024

Date accepted : 01 April 2024

Page count

Figures: 0, Tables: 5, References: 42, Pages: 11