Functional polymorphism in H2BFWT-5′UTR is associated with susceptibility to male infertility

Jinu Lee, Hee Suk Park, Hwan Hee Kim, Yeo Jin Yun, Dong Ryul Lee, Suman Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1942-1951
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number8 B
DOIs
Publication statusPublished - 2009 Aug 1

Fingerprint

5' Untranslated Regions
Male Infertility
Histones
Testis
Spermatozoa
Open Reading Frames
Sperm Count
Genes
Chromatin
Single Nucleotide Polymorphism
Western Blotting
Genotype
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

Cite this

Lee, Jinu ; Park, Hee Suk ; Kim, Hwan Hee ; Yun, Yeo Jin ; Lee, Dong Ryul ; Lee, Suman. / Functional polymorphism in H2BFWT-5′UTR is associated with susceptibility to male infertility. In: Journal of Cellular and Molecular Medicine. 2009 ; Vol. 13, No. 8 B. pp. 1942-1951.
@article{401e5bc4f67b40af9ab1039303816f47,
title = "Functional polymorphism in H2BFWT-5′UTR is associated with susceptibility to male infertility",
abstract = "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.",
author = "Jinu Lee and Park, {Hee Suk} and Kim, {Hwan Hee} and Yun, {Yeo Jin} and Lee, {Dong Ryul} and Suman Lee",
year = "2009",
month = "8",
day = "1",
doi = "10.1111/j.1582-4934.2009.00830.x",
language = "English",
volume = "13",
pages = "1942--1951",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "8 B",

}

Functional polymorphism in H2BFWT-5′UTR is associated with susceptibility to male infertility. / Lee, Jinu; Park, Hee Suk; Kim, Hwan Hee; Yun, Yeo Jin; Lee, Dong Ryul; Lee, Suman.

In: Journal of Cellular and Molecular Medicine, Vol. 13, No. 8 B, 01.08.2009, p. 1942-1951.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional polymorphism in H2BFWT-5′UTR is associated with susceptibility to male infertility

AU - Lee, Jinu

AU - Park, Hee Suk

AU - Kim, Hwan Hee

AU - Yun, Yeo Jin

AU - Lee, Dong Ryul

AU - Lee, Suman

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=72949118097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72949118097&partnerID=8YFLogxK

U2 - 10.1111/j.1582-4934.2009.00830.x

DO - 10.1111/j.1582-4934.2009.00830.x

M3 - Article

C2 - 19583817

AN - SCOPUS:72949118097

VL - 13

SP - 1942

EP - 1951

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 8 B

ER -