title: Effects of maternal 5,10-methylenetetrahydrofolate reductase C677T and A1298C Polymorphisms and tobacco smoking on infant birth weight in a Japanese population.
abstract: BACKGROUND
  Intracellular folate hemostasis depends on the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Because 5,10-MTHFR 677TT homozygosity and tobacco smoking are associated with low folate status, we tested the hypothesis that smoking in mothers with 5,10-MTHFR C677T or A1298C polymorphisms would be independently associated with lower birth weight among their offspring.
  
  
  METHODS
  We assessed 1784 native Japanese mother-child pairs drawn from the ongoing birth cohort of The Hokkaido Study on Environment and Children's Health. Data (demographic information, hospital birth records, and biological specimens) were extracted from recruitments that took place during the period from February 2003 to March 2006. Maternal serum folate were assayed by chemiluminescent immunoassay, and genotyping of 5,10-MTHFR C677T/A1298C polymorphisms was done using a TaqMan allelic discrimination assay.
  
  
  RESULTS
  The prevalence of folate deficiency (<6.8 nmol/L) was 0.3%. The 5,10-MTHFR 677CT genotype was independently associated with an increase of 36.40 g (95% CI: 2.60 to 70.30, P = 0.035) in mean infant birth weight and an increase of 90.70 g (95% CI: 6.00 to 175.50, P = 0.036) among male infants of nonsmokers. Female infants of 677TT homozygous passive smokers were 99.00 g (95% CI: -190.26 to -7.56, P = 0.034) lighter. The birth weight of the offspring of smokers with 5,10-MTHFR 1298AA homozygosity was lower by 107.00 g (95% CI: -180.00 to -33.90, P = 0.004).
  
  
  CONCLUSIONS
  The results suggest that, in this population, maternal 5,10-MTHFR C677T polymorphism, but not the 5,10-MTHFR A1298C variant, is independently associated with improvement in infant birth weight, especially among nonsmokers. However, 5,10-MTHFR 1298AA might be associated with folate impairment and could interact with tobacco smoke to further decrease birth weight.
authors.affiliation: Department of Public Health Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Thamar Ayo
authors.initials: TA
authors.lastname: Yila
authors.forename: Seiko
authors.initials: S
authors.lastname: Sasaki
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyashita
authors.forename: Titilola Serifat
authors.initials: TS
authors.lastname: Braimoh
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kashino
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Emiko
authors.initials: E
authors.lastname: Okada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Baba
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshioka
authors.forename: Hisanori
authors.initials: H
authors.lastname: Minakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Endo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sengoku
authors.forename: Reiko
authors.initials: R
authors.lastname: Kishi
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001724:Birth Weight / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005494:Folic Acid Deficiency / Q000208:ethnology / Q000209:etiology / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000208:ethnology / Q000235:genetics; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology / Q000235:genetics
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)