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Background  Methylenetetrahydrofolate reductase ( MTHFR ) C677T, A1298C and methionine synthase reductase ( MTRR ) A66G polymorphisms are important genetic determinants for homocysteine (Hcy) levels, and are associated with several disorders. These polymorphisms are heterogeneously distributed worldwide. Our objective was to explore the geographical distributions of these polymorphisms in China.    Methodologies  15357 healthy adults were recruited from 10 regions. Buccal samples were collected and genomic DNA was isolated. Genotyping was performed using the fluorogenic 5′-nuclease assay.    Principal Findings  The prevalence of the three polymorphisms among different populations from China varied significantly and showed apparent geographical gradients. For  MTHFR  C677T, the frequencies of the 677T allele and the 677TT genotype were significantly higher among northern populations and ranged from the lowest values (24.0% and 6.4%, respectively) in Hainan (southern) to the highest values (63.1% and 40.8%, respectively) in Shandong (northern). For  MTHFR  A1298C, the 1298C allele and the 1298CC genotype frequencies were significantly higher among southern populations and increased from low values (13.1% and 1.4%, respectively) in Shandong to high values (25.7% and 6.7%, respectively) in Hainan. For A66G, the 66G allele and the 66GG genotype frequencies increased from lower values (23.7% and 5.4%, respectively) in Shandong to higher values (29.2% and 8.6%, respectively) in Hainan. The overall frequency of the 677T allele, 677TT genotype, 1298C allele, 1298CC genotype, 66G allele and 66GG genotype in the Chinese Han population was 45.2%, 23.2%, 18.6%, 3.9%, 25.7%, and 6.6%, respectively. No gender differences were found in the prevalence of both the  MTHFR  C677T and  MTRR  A66G polymorphisms.    Conclusions  This study indicates that there are marked geographical variations in the prevalence of the three polymorphisms among Chinese Han populations. Our baseline data may be useful for future researches in related fields.

Geographical Distribution of MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in China: Findings from 15357 Adults of Han Nationality