title: MTHFR, MTR and MTRR polymorphisms and risk of chronic kidney disease in Japanese: cross-sectional data from the J-MICC Study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan, a-hishi@med.nagoya-u.ac.jp.
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Yin
authors.initials: Y
authors.lastname: Guang
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tanvir Chowdhury
authors.initials: TC
authors.lastname: Turin
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hideshi
authors.initials: H
authors.lastname: Niimura
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.forename: Jun
authors.initials: J
authors.lastname: Otonari
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.forename: Sakurako
authors.initials: S
authors.lastname: Katsuura
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000368:Aged; D000428:Alcohol Drinking; D044466:Asian People / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004032:Diet; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
chemical_list: D005492:Folic Acid; D003404:Creatinine; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human