Purpose: Chronic kidney disease (CKD) is well known as a strong risk factor for both of end-stage renal disease and cardiovascular disease. To clarify the associations of MTHFR, MTR, and MTRR polymorphisms with the risk of CKD in Japanese, we examined this association among Japanese subjects using cross-sectional data. Methods: The subjects for this analysis were 3,318 participants consecutively selected from the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. The polymorphisms were genotyped by a multiplex polymerase chain reaction-based Invader assay. Age- and sex-adjusted odds ratio (aOR) of CKD with stage 3-5 was calculated for each genotype. Results: When those with MTHFR C677T C/C were defined as references, those with MTHFR C677T C/T and T/T demonstrated the aORs for CKD of 1.14 (95 % CI 0.93-1.40) and 1.39 (1.06-1.82), respectively. Marginally significantly decreased risk of CKD with increasing number of MTR A2756G G allele (p = 0.058) was observed. Stratified analyses by plasma folate low (<7.4 ng/ml) or high (≥7.4 ng/ml) suggested significantly higher OR of CKD for those with MTHFR C677T T/T and low serum folate with the aOR of 2.07 (95 % CI 1.30-3.31) compared with that for those with MTHFR C677T T/T and high serum folate. Conclusions: The present study found a significant association between the subjects with the T/T genotype of MTHFR C677T polymorphism and the elevated risk of CKD, which may suggest the possibility of the risk evaluation and prevention of this potentially life-threatening disease based on genetic traits in the near future.
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