After adjusting for non-modifiable and modifiable risk factors of type 2 diabetes, HRs for incident risk of type 2 diabetes were 0.29 (0.14, 0.57) and 0.31 (0.18, 0.53), respectively, for participants with high serum betaine levels (>47.82 μmol/L) and heterozygous or homozygous variants (GA and AA for MTHFR G1793A, AC and CC for MTHFR A1298C), where the low serum betaine levels (≤47.82 μmol/L) and normal type genotype (GG for MTHFR G1793A, AA for MTHFR A1298C) was the reference category. The gene discussed is MTHFR; the disease is type 2 diabetes mellitus.