Targeted Next-Generation Sequencing Identifies Novel Sequence Variations of Genes Associated with Nonobstructive Azoospermia in the Han Population of Northeast China

BACKGROUND: This study aimed to screen common and low-frequency variants of nonobstructive azoospermia (NOA)-associated genes, and to construct a database for NOA-associated single nucleotide variants (SNVs). MATERIAL/METHODS: Next-generation sequencing of 466 NOA-associated genes was performed in 34 patients with NOA (mean age, 29.06±4.49 years) and 40 sperm donors (mean age, 25.08±5.75 years) from the Han population of northeast China. The SNV database was constructed by summarizing NOA non-negatively-associated SNVs showing statistical differences between NOA cases and controls, and then selecting low-frequency variants using Baylor’s pipeline, to identify statistically valid SNVs. RESULTS: There were 65 SNVs identified that were significantly different between both groups (p<0.05). Five genetic variants showed positive correlations with NOA: MTRR c.537T>C (rs161870), odds ratios (OR), 3.686, 95% confidence interval (CI), 1.228–11.066; MTRR, c.1049A>G (rs162036), OR, 3.686, 95% CI, 1.228–11.066; PIWIL1, c.1580G>A (rs1106042), OR, 4.737, 95% CI, 1.314–17.072; TAF4B, c.1815T>C (rs1677016), OR, 3.599, 95% CI, 1.255–10.327; and SOX10 c.927T>C (rs139884), OR, 3.192, 95% CI, 1.220–8.353. Also, 52 NOA non-negatively associated SNVs and 39 SNVs were identified by Baylor’s pipeline and selected for the SNV database. CONCLUSIONS: Five genetic variants were shown to have positive correlations with NOA. The SNV database constructed contained NOA non-negatively associated SNVs and low-frequency variants. This study showed that this approach was an effective strategy to identify risk alleles of NOA.