Fahrul Nurkolis, Nurlinah Amalia, Yosi Yohanes Putra Tandi, Ariq Fadhil Athallah, Muhammad Reva Aditya, Ammar Nojaid, Farizky Martriano Humardani, Achmad Fabiansyah Prapriatna, Nurpudji Astuti Taslim, Dante Saksono Harbuwono, Raymond Rubianto Tjandrawinata
The rs1801133 (C677T) polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been linked to type 2 diabetes (T2D) risk. This study aimed to assess the association between rs1801133 genotypes (CC, CT, TT) and T2D across multiethnic populations and to identify genotype- and region-specific risks. A global meta-epidemiological analysis was conducted using data from 19 studies comprising 6479 participants from Asia, Africa, Europe, and America. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses by region were also performed. The results of the CC vs. CT dominant genetic model were OR 95% CI = 0.63 (0.46–0.87); p = 0.005; the CC vs. TT genetic recessive model yielded OR 95% CI = 0.59 (0.38–0.91); p = 0.02; and the CT vs. TT codominance genetic model yielded OR 95% CI = 0.95 (0.65–1.37); p = 0.78. Based on the subgroup analysis, the CC genotype is predominantly associated with an increased risk of T2D in both Africa and Europe. From this study, the CC genotype was proven to be highly contributory to T2D risk compared to the CT and TT genotypes. These findings highlight the need for ethnicity-informed genetic screening and targeted prevention strategies in global diabetes management. © 2025 by the authors.
Faculty of Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia; Medical Research Center of Indonesia, Surabaya, 60281, Indonesia; Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia; Medical Study Program, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Master Program of Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Internal Medicine, Dr. Cipto Mangunkusumo National Central Hospital, Jakarta, 10430, Indonesia; Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, 90245, Indonesia; Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Dr. Cipto Mangunkusumo National Referral Hospital, Jakarta, 10430, Indonesia; Metabolic, Cardiovascular and Aging Cluster, The Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; Center for Pharmaceutical and Nutraceutical Research and Policy, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia
