Genetic association study ofRNF8andBRDTvariants with non-obstructive azoospermia in the Chinese Han population

Abstract

Increasing evidence indicates that polymorphisms in genes relevant to spermatogenesis might modulate the efficiency of reproduction in men. Ring finger protein 8 (RNF8) and bromodomain testis-specific (BRDT) are two candidate genes associated with spermatogenesis. Here, we considered potential associations of 14 single nucleotide polymorphisms (SNPs) in RNF8 and BRDT genes in Chinese patients with non-obstructive azoospermia (NOA). We analyzed 361 men with NOA and 368 fertile controls by using Sequenom iplex technology. Our data did not reveal any variants associated with NOA susceptibility. However, we observed that rs104669 and rs195432 of RNF8 were in strong linkage disequilibrium. Haplotype analysis of the two SNPs indicated that the haplotype AC reduced the risk of NOA and the haplotype TC significantly evaluated the risk of NOA. Moreover, the RNF8 variants rs195432 (C/A p ¼ 0.030), rs195434 (T/C p ¼ 0.025), and rs2284922 (T/C p ¼ 0.034) were correlated with the smaller testis volume.Abbreviations: RNF8: ring finger protein 8; BRDT: bromodomain testis-specific; SNPs: single nucleotide polymorphisms; NOA: non-obstructive azoospermia; HWE: Hardy Weinberg Equilibrium; OR: odds ratio; LD: linkage disequilibrium; MAF: minor allele frequency(ies) Keywords BRDT, male infertility, non-obstructive azoospermia, RNF8, single nucleotide polymorphisms (SNPs) History

Whole-exome sequencing identified a homozygous BRDT mutation in a patient with acephalic spermatozoa

“…However, another study that consisted of 276 azoospermic and 182 fertile men of Arab and Jewish descent, demonstrated no association between BRDT rs3088232 and infertility [21]. Another Chinese group analyzed 361 men with non-obstructive azoospermia (NOA) and 368 fertile controls, and they could not find any BRDT variants associated with NOA susceptibility [22]. Thus, the association of BRDT with male infertility is inconclusive.…”

Upregulation of the RNF8 gene can predict the presence of sperm in azoospermic individuals

“…This study is the first to report the upregulation of RNF8 expression using RT-qPCR, However, a microarray study by Spiess et al [31] showed significantly higher expression of RNF8 in individuals with Sertoli cell-only syndrome histology than in men with normal spermatogenesis. Moreover, a haplotype analysis of rs104669 and rs195432 of RNF8, which were in strong linkage disequilibrium, revealed that the AC haplotype was correlated with a reduced risk of NOA and smaller testis volume in a Chinese population [32]. Considering the elevated level of RNF8 expression in the patients with im-paired spermatogenesis in this study, this alteration likely reflects changes in somatic cells, which may imply that RNF8 has potential for interventional therapies [33].…”