MTHFR polymorphisms, inadequate folate intake, and anemia between stunted and non-stunted children in East Lombok, Indonesia

Dwi Yanti (Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia)
Min Kyaw Htet (Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia)
Paul Haggarty (Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD, UK)
Umi Fahmida (Department of Nutrition, Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia)
Asmarinah

Paediatrica Indonesiana
Vol. 66 No. 5 (2026): September 2026

Background Folate supports one-carbon metabolism, which is important for DNA synthesis and methylation reactions, but is often under-emphasized in stunting-related nutrition programs. Common methylenetetrahydrofolate reductase (MTHFR) polymorphisms may influence folate metabolism when dietary folate intake is inadequate. Objective To analyze  MTHFR C677T and A1298C polymorphisms, inadequate folate intake, and anemia status between young children with and without stunting in East Lombok, Indonesia. Methods This analysis included 299 children aged 18–23.9 months, consisting of 149 stunted and 150 non-stunted children. Dietary intake was assessed using two non-consecutive 24-hour recalls. MTHFR polymorphisms were genotyped using TaqMan allelic discrimination assays. Hemoglobin was measured using an automated analyzer and logistic regression was used to analyze for factors associated with stunting and anemia. Results Genotype data were available for 299 children. For C677T, 29.1% carried CT/TT, while for A1298C, 55.8% carried AC/CC. Folate intake below the recommended requirement was common in both stunted and non-stunted children (89.3% and 86.0%, respectively), while vitamin B12 inadequacy was uncommon 6.7% for both groups). Anemia, defined as hemoglobin <10.5 g/dL, was more frequent among stunted children (34.9% vs. 22.8%, respectively; P=0.02). MTHFR genotype, folate intake, riboflavin intake, iron intake, age, and sex were not associated with stunting. Birth weight was strongly associated with stunting (P<0.001), while age (P=0.004) and sex (P=0.03) were associated with anemia. MTHFR genotype and folate intake were not directly associated with either stunting or anemia. Conclusion MTHFR C677T CT/TT and A1298C AC/CC carriage and folate intake inadequacy were common but not stunting-specific. The absence of genotype differences and the strong birth weight association suggest an explanatory gap beyond current dietary and genetic indicators, supporting future studies incorporating folate biomarkers, anemia-related pathways, and DNA methylation profiles.