Genetic variants in Ser-Arg protein-coding genes are associated with the risk of nonobstructive azoospermia in Chinese men

Abstract

Objective: To evaluate the association between genetic variants in Ser-Arg (SR) protein-coding genes and the susceptibility of nonobstructive azoospermia (NOA) in Chinese men.

Design: Case-control study.

Setting: State Key Laboratory of Reproductive Medicine in Nanjing Medical University conducted the genotyping and examined the expression levels of genes.

Patient(s): The study included 962 NOA patients and 1,931 control subjects.

Intervention(s): None.

Main outcome measure(s): Genotyping of 16 single-nucleotide polymorphisms (SNPs) of eight "canonic" SR protein-coding genes were performed with the use of the Illumina Infinium Beadchip platform. Odds ratios were calculated by logistic regression analysis in the additive model. Expression levels were measured by quantitative reverse-transcription polymerase chain reaction.

Result(s): Rs17431717 near SFRS9 and rs12046213 near SFRS4 were significantly associated with a decreased risk of NOA, whereas rs10849753 near SFRS9 and rs6103330 in SFRS6 were associated with an increased risk of NOA. Of the two SNPs in SFRS9, only rs17431717 remained significant after conditioning on another. Combined analysis of three promising SNPs (rs17431717, rs12046213, and rs6103330) showed that compared with individuals with "0-2" risk alleles, those carrying "3," "4," and "≥ 5" risk alleles had 1.22-, 1.38-, and 1.90-fold increased risk of NOA, respectively.

Conclusion(s): Polymorphisms in SR protein-coding genes may contribute to the risk of NOA in Chinese men. The findings of this study can help us to further understand the etiology of spermatogenic impairment, and they provide more evidence for the role of splicing activity in human spermatogenesis.

Keywords: NOA; SR protein family; alternative splicing; susceptibility.