Diabetes, Metabolic Syndrome and Obesity (Apr 2024)
Serum Folate and Vitamin B12 Modify the Associations of N6AMT1 Genetic Variants with Gestational Diabetes Mellitus: A Cross-Sectional Study in Chinese Pregnant Women
Abstract
Guanshuai Guo,1,2,* Xi Chen,1,2,* Jingran Zhang,1,2 Xiangmin Meng,3 Aifeng Jia,4 Xinli Xing,5 Fenglei Huang,6 Xumei Zhang,2,7 Juan Liu,8 Shuying Li,3,9 Qiang Zhang1,2 1Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, People’s Republic of China; 4Department of Obstetrics and Gynecology, Tianjin Xiqing Hospital, Tianjin, People’s Republic of China; 5Department of Obstetrics and Gynecology, Women’s and Children’s Health Center of Dongchangfu District, Liaocheng, People’s Republic of China; 6Department of Reproductive Health, Women’s and Children’s Health Center of Dongchangfu District, Liaocheng, People’s Republic of China; 7Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 8Department of Biomedical Information and Library, Tianjin Medical University, Tianjin, People’s Republic of China; 9NHC 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*These authors contributed equally to this workCorrespondence: Shuying Li, Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, 300380, People’s Republic of China, Email [email protected] 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 [email protected]: 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 B12.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 B12, 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 B12 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 B12 are more prone to GDM. The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B12 (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 B12 levels can modify their associations.Keywords: N6AMT1, folate, vitamin B12, gene-nutrition interaction, gestational diabetes mellitus
