Relation of nitric oxide synthase gene (NOS3) polymorphisms to varicocele risk and post-varicocelectomy seminal oxidative stress reduction

Andrologia. 2020 Apr;52(3):e13525. doi: 10.1111/and.13525. Epub 2020 Feb 5.

Abstract

The pathophysiology of varicocele remains to be unknown. Several genetic factors have been implicated in varicocele etiopathogenesis. We studied the relationship between NOS3 c.894G>T, c.786T>C and 4b/a polymorphisms to varicocele risk and their prognostic value as regards improvement of the post-operative seminal parameters &/or seminal malonaldehyde levels. The three NOS3 polymorphisms were evaluated in 100 patients with varicocele and 100 healthy subjects by RT-PCR. Seminal plasma MDA level was measured pre-operatively and 3 months after varicocelectomy by the thiobarbituric acid method. The GT, TT, TC and bb genotypes of NOS3 polymorphism were more commonly observed in varicocele patients (30%, 9%, 28% and 70% respectively) compared to normal controls (12%, 0%, 10% and 50% respectively). The mean percentage of post-varicocelectomy seminal MDA reduction was highest with the GT genotype (p < .001). Genotypes GT+TT, TC and bb were associated with varicocele occurrence in our patients. The T (c.894G>T), C (c.786T>C) and b (NOS3 intron 4 VNTR) alleles were significantly associated with varicocele occurrence in our cohort of patients. We also report a better response regarding the reduction of seminal MDA after varicocelectomy with the GT and ba genotypes.

Keywords: NO; NOS3; male infertility; varicocoele.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Infertility, Male / genetics
  • Infertility, Male / pathology
  • Infertility, Male / prevention & control*
  • Male
  • Malondialdehyde / analysis
  • Malondialdehyde / metabolism
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Oxidative Stress / genetics
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Semen / metabolism
  • Spermatic Cord / blood supply
  • Spermatic Cord / surgery
  • Treatment Outcome
  • Urologic Surgical Procedures, Male*
  • Varicocele / epidemiology
  • Varicocele / genetics*
  • Varicocele / surgery
  • Vascular Surgical Procedures*

Substances

  • Malondialdehyde
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III