Relationship of SNP of H2BFWT gene to male infertility in a Chinese population with idiopathic spermatogenesis impairment

Abstract

The H2B family, member W, testis specific (H2BFWT) gene encodes a testis specific histone that plays a crucial role in reorganization and remodeling of chromatin and epigenetic regulation during spermatogenesis, suggesting that the gene may be involved in spermatogenesis impairment. To test the speculation, the allele and haplotype frequencies of two single-nucleotide polymorphism loci in this gene, -9C>T and 368A>G, were investigated in 409 infertile patients with idiopathic azoospermia or oligozoospermia and 209 fertile men as controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. As the results, the frequencies of -9T (52.8% vs. 41.6%, p = 0.009) and 368G (43.0% vs. 32.5%, p = 0.012) were significantly higher in patients than those in controls; after stratifying patients, the significant higher frequencies were still detected in allele -9T for azoospermia (57.4% vs. 41.6%, p = 0.001) and allele 368G for oligozoospermia (45.4% vs. 32.5%, p = 0.007). The haplotype CA was significantly decreased (22.8% vs. 33.0%, p = 0.006) whereas TG was significantly increased (18.3% vs. 7.2%, p < 0.001) in infertile patients compared with controls. These results indicated that the polymorphism -9C>T and 368A>G in H2BFWT gene are associated with male infertility with idiopathic azoospermia or oligozoospermia, suggesting that H2BFWT gene might be contribute to susceptibility to spermatogenesis impairment in Chinese population.

Essential Role of Histone Replacement and Modifications in Male Fertility

“…In humans, H2BFWT is a testis-specific histone, is synthesized and aggregated in testes, and single nucleotide polymorphisms (SNPs) in this gene is highly associated with male infertility (Churikov et al, 2004; Lee et al, 2009; Ying et al, 2012; Rafatmanesh et al, 2018; Teimouri et al, 2018). And spermatid-specific H2B (ssH2B) and H2BL1 have been identified and are strongly enriched in round or elongating spermatids, similar to that of TPs and protamines (Moss and Orth, 1993; Unni et al, 1995; Govin et al, 2007).…”

Genetics of male infertility: from research to clinic

“…This SNP maps to the 5'UTR of H2BFWT and has been demonstrated to affect the translation of the protein (Lee et al 2009). The two case-control studies found significant association (with moderate OR ranging from 1.51-1.88) with completely different semen phenotypes: azoospermia in the Chinese population (Ying & Scott 2012) whereas lack of association with azoospermia and association with non-azoospermia (a heterogenous group of oligo/ astheno/teratozoospermic men) in the Korean study (Lee et al 2009). Such contradictory results clearly discourage further studies on this SNP.…”

Primate-specific histone variants

“…Several studies have suggested a relationship between single nucleotide polymorphisms (SNPs) in H2BFWT and defects in male fertility (Lee et al 2009;Rafatmanesh et al 2018;Ying et al 2012). In particular, three groups have linked the -9C > T mutation (rs7885967) within the 5' untranslated region of H2BFWT to nonazoospermia (p = 0.018), a reduced sperm count (p = 0.0127) and a weakened sperm vitality (p = 0.0076) (Lee et al 2009;Rafatmanesh et al 2018;Ying et al 2012). A related investigation by Ying et al revealed that the 368A > G mutation (rs553509) increased the risk of male sterility (Ying et al 2012) (Figure 2).…”