PMID- 19583817
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20211020
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 13
IP  - 8B
DP  - 2009 Aug
TI  - Functional polymorphism in H2BFWT-5'UTR is associated with susceptibility to male 
      infertility.
PG  - 1942-1951
LID - 10.1111/j.1582-4934.2009.00830.x [doi]
AB  - H2B histone family, member W, testis-specific (H2BFWT) gene encodes a 
      testis-specific histone that becomes incorporated into sperm chromatin. A male 
      infertility-associated single nucleotide polymorphism (-9C > T) within the 5' 
      untranslated region (5'UTR) of the H2BFWT gene was identified by direct 
      sequencing. Statistical association studies showed the polymorphism significantly 
      associated with male infertility (n = 442, P = 0.0157), especially in 
      non-azoospermia (n = 262, P = 0.018). Furthermore, this polymorphism is also 
      associated with sperm parameters, especially sperm count (n = 164, P = 0.0127) 
      and vitality (n = 164, P = 0.0076). We investigated how the genetic variant at 
      5'UTR confers susceptibility to non-azoospermia. Western blotting of His-tag 
      H2BFWT revealed a difference at the translational level between -9T and the 
      wild-type -9C in the absence of change at the transcriptional level. Reporter 
      assays showed that this reducing translational change originated from an upstream 
      open reading frame (uORF) generated by the -9C to -9T change. Finally, in vivo 
      H2BFWT expression in sperm was significantly dependent on the -9C > T genotype 
      from non-azoospermia (P = 0.0061). Therefore, this polymorphism could affect the 
      translational efficiency of a quantitatively important histone protein by the 
      uORF. Our data implicate H2BFWT as a susceptibility factor for male infertility, 
      possibly with other genetic and environmental factors.
FAU - Lee, Jinu
AU  - Lee J
AD  - Department of Pharmacology, CHA Stem Cell Institute, School of Medicine, CHA 
      University, Kyunggi-Do, Korea.
FAU - Park, Hee Suk
AU  - Park HS
AD  - Functional Genomics Lab, CHA Stem Cell Institute, School of Medicine, CHA 
      University, Kyunggi-Do, Korea.
FAU - Kim, Hwan Hee
AU  - Kim HH
AD  - Functional Genomics Lab, CHA Stem Cell Institute, School of Medicine, CHA 
      University, Kyunggi-Do, Korea.
FAU - Yun, Yeo-Jin
AU  - Yun YJ
AD  - Functional Genomics Lab, CHA Stem Cell Institute, School of Medicine, CHA 
      University, Kyunggi-Do, Korea.
FAU - Lee, Dong Ryul
AU  - Lee DR
AD  - Fertility Center of CHA General Hospital, CHA Stem Cell Institute, School of 
      Medicine, CHA University, Seoul, Korea.
FAU - Lee, Suman
AU  - Lee S
AD  - Functional Genomics Lab, CHA Stem Cell Institute, School of Medicine, CHA 
      University, Kyunggi-Do, Korea.
AD  - Department of Pharmacology, CHA Stem Cell Institute, School of Medicine, CHA 
      University, Kyunggi-Do, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090706
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (5' Untranslated Regions)
RN  - 0 (DNA Primers)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Base Sequence
MH  - Blotting, Western
MH  - Case-Control Studies
MH  - DNA Primers
MH  - Humans
MH  - Infertility, Male/*genetics
MH  - Male
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Genetic
PMC - PMC6529973
EDAT- 2009/07/09 09:00
MHDA- 2010/07/20 06:00
PMCR- 2009/08/01
CRDT- 2009/07/09 09:00
PHST- 2009/07/09 09:00 [entrez]
PHST- 2009/07/09 09:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
PHST- 2009/08/01 00:00 [pmc-release]
AID - JCMM830 [pii]
AID - 10.1111/j.1582-4934.2009.00830.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2009 Aug;13(8B):1942-1951. doi: 10.1111/j.1582-4934.2009.00830.x. 
      Epub 2009 Jul 6.