title: Dual Effects of a RETN Single Nucleotide Polymorphism (SNP) at -420 on Plasma Resistin: Genotype and DNA Methylation.
abstract: BACKGROUND
  We previously reported that single nucleotide polymorphism (SNP)-420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of cytosine-phosphate-guanine dinucleotides.
  
  
  OBJECTIVE
  To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420.
  
  
  METHODS
  Genomic DNA was extracted from peripheral white blood cells in 2078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after DNA bisulfite conversion.
  
  
  RESULTS
  Methylation at SNP-420 was highest in the C/C genotype (36.9 ± 5.7%), followed by C/G (21.4 ± 3.5%) and G/G (2.9 ± 1.4%; P < 0.001). When assessed in each genotype, methylation at SNP-420 was inversely associated with plasma resistin in the C/C (β = -0.134, P < 0.001) or C/G (β = -0.227, P < 0.001) genotype. In THP-1 human monocytes intrinsically having the C/C genotype, a demethylating reagent, 5-aza-dC, decreased the methylation at SNP-420 and increased RETN messenger RNA. SNP+1263 (rs3745369), located in the 3' untranslated region of RETN, was also associated with methylation at SNP-420. In addition, highly sensitive C-reactive protein was inversely associated with methylation at SNP-420 in the C/C genotype, whereas body mass index was positively associated.
  
  
  CONCLUSIONS
  Plasma resistin was inversely associated with the extent of methylation at SNP-420 mainly dependent on the SNP-420 genotype. The association can also be explained partially independent of SNP-420 genotypes. SNP-420 could have dual, genetic and epigenetic effects on plasma resistin.
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onuma
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; and.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Kawamura
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-8654, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishida
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Takata
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ochi
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishimiya
authors.affiliation: Geriatric Medicine, and.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ohyagi
authors.affiliation: Community Medicine, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kawamoto
authors.affiliation: Geriatric Medicine, and.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.affiliation: Geriatric Medicine, and.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.affiliation: Departments of Diabetes and Molecular Genetics.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Osawa
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D052243:Resistin / Q000097:blood / Q000235:genetics*
chemical_list: C499624:RETN protein, human; D012333:RNA, Messenger; D052243:Resistin; D002097:C-Reactive Protein