title: Lack of association of MTHFR rs1801133 polymorphism and CTCFL mutations with sperm methylation errors in infertile patients.
abstract: OBJECTIVE
  To find out whether the MTHFR rs1801133 polymorphism is a risk factor for male infertility in the Spanish population. To determine if a pattern of sperm DNA hypomethylation at the paternally imprinted loci H19-ICR and/or IG-DMR is related to the MTHFR rs1801133 polymorphism and/or CTCFL mutations.
  
  
  METHODS
  One hundred and seven samples from individuals who sought consultation for fertility problems and twenty-five semen samples from sperm donors were analyzed. The MTHFR rs1801133 SNP was analyzed in all samples by the PCR-RFLP method. We compared the distribution of the genotypes between control and infertile populations and among the groups of patients with altered seminal parameters. In those patients with the most severe hypomethylation pattern (n = 12) we also analyzed the CTCFL protein-coding exons by sequencing.
  
  
  RESULTS
  There were no significant differences in the distribution of the genotypes among the control and infertile populations. Moreover, none of the genotypes were associated, neither to the characteristics of the seminogram, nor to the presence of sperm DNA hypomethylation. We did not identify frameshift, nonsense or missense mutations of the CTCFL gene.
  
  
  CONCLUSIONS
  The MTHFR rs1801133 polymorphism is not associated with male infertility in the Spanish population. Neither the MTHFR polymorphism, nor CTCFL mutations explain a pattern of sperm hypomethylation at paternally imprinting loci.
authors: Unitat de Biologia Cellular, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain.
authors: Cristina
authors: C
authors: Camprubí
authors: Marta
authors: M
authors: Pladevall
authors: Mark
authors: M
authors: Grossmann
authors: Nicolás
authors: N
authors: Garrido
authors: Maria C
authors: MC
authors: Pons
authors: Joan
authors: J
authors: Blanco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology
chemical_list: C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
references: Fertil Steril. 2003 Nov;80(5):1190-4
references: 14607573
references: Epigenetics. 2012 Oct;7(10):1115-24
references: 22885410
references: Genet Test Mol Biomarkers. 2011 Mar;15(3):153-7
references: 21138341
references: Genomics. 2000 May 1;65(3):293-8
references: 10857753
references: Sex Dev. 2011;5(2):60-9
references: 21293114
references: PLoS Biol. 2006 Oct;4(11):e355
references: 17048991
references: Fertil Steril. 2010 Oct;94(5):1728-33
references: 19880108
references: Nat Genet. 1995 May;10(1):111-3
references: 7647779
references: Reproduction. 2011 Jun;141(6):749-57
references: 21389080
references: Hum Reprod. 2006 Dec;21(12):3162-70
references: 16861746
references: Int J Androl. 2012 Feb;35(1):18-24
references: 21535009
references: PLoS One. 2009 Aug 06;4(8):e6540
references: 19657388
references: Mol Hum Reprod. 2007 Apr;13(4):213-22
references: 17277043
references: Int J Androl. 2010 Aug 1;33(4):642-9
references: 19878521
references: Int J Androl. 2005 Apr;28(2):115-9
references: 15811073
references: Eur J Hum Genet. 2009 Dec;17(12):1582-91
references: 19471309
references: N Engl J Med. 2001 Apr 12;344(15):1172-3
references: 11302150
references: Fertil Steril. 2010 Jul;94(2):585-94
references: 19338988
references: Hum Mol Genet. 2007 Nov 1;16(21):2542-51
references: 17636251
references: Asian J Androl. 2007 Jan;9(1):57-62
references: 16888682
references: PLoS One. 2011;6(7):e22277
references: 21799811
references: Lancet. 2004 May 22;363(9422):1700-2
references: 15158633
references: Reprod Sci. 2011 Mar;18(3):304-15
references: 20978181
references: J Endocrinol Invest. 2003 Jul;26(7):620-2
references: 14594111
references: J Assist Reprod Genet. 2005 Oct;22(9-10):361-8
references: 16247718
references: Biomarkers. 2006 Jan-Feb;11(1):53-60
references: 16484136
references: Mol Hum Reprod. 2008 Feb;14(2):67-74
references: 18178607
references: Eur J Hum Genet. 2010 Jan;18(1):73-80
references: 19584898