Association between recurrent aphthous stomatitis and inheritance of a single-nucleotide polymorphism of the NOS2 gene encoding inducible nitric oxide synthase

J Oral Pathol Med. 2011 Oct;40(9):715-20. doi: 10.1111/j.1600-0714.2011.01039.x. Epub 2011 Apr 11.


Background: Recurrent aphthous stomatitis is a common ulcerative disease of the oral mucosa. Recurrent oral aphthous ulceration is also a feature of the more serious and systemic Behçet's disease. Nitric oxide is a free radical synthesized by one of a family of nitric oxide synthase (NOS) enzymes and is an important regulator of inflammation and immunity. Association of NOS3 gene polymorphisms encoding endothelial nitric oxide synthase has been reported in Behçet's disease but not recurrent aphthous stomatitis. The aim of this study was to investigate any association between NOS2 gene polymorphisms that encode inducible nitric oxide synthase and recurrent aphthous stomatitis.

Methods: This is a case control association study. Eighty-three Jordanian recurrent aphthous stomatitis patients and 83 age, gender and ethnically matched controls were genotyped for three NOS2 single-nucleotide polymorphisms, rs10459953, rs1060822 and rs2297518. Chi-squared analysis was used to compare the allele frequencies and genotypes.

Results: There was a significant association between recurrent aphthous stomatitis and inheritance of single-nucleotide polymorphism rs2297518 (P = 0.006). Although no direct association was demonstrated between rs10459953 or rs1060822 and recurrent aphthous stomatitis, a strong linkage disequilibrium was identified between rs1060822 and rs2297518.

Conclusion: Inheritence of a NOS2 single-nucleotide polymorphism rs2297518 is associated with increased risk of recurrent aphthous stomatitis in a Jordanian population. Confirmatory studies in other populations and investigation of other NOS2 gene polymorphisms will enhance our understanding of the functional basis of this association and help elucidate the role of inducible nitric oxide synthase in recurrent aphthous stomatitis.

Publication types

  • Comparative Study

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adenine
  • Adult
  • Case-Control Studies
  • Cytosine
  • Ethnicity / genetics
  • Exons / genetics
  • Female
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Frequency / genetics
  • Genotype
  • Guanine
  • Haplotypes / genetics
  • Humans
  • Jordan
  • Linkage Disequilibrium / genetics
  • Male
  • Nitric Oxide Synthase Type II / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Recurrence
  • Stomatitis, Aphthous / enzymology*
  • Stomatitis, Aphthous / genetics
  • Thymine


  • 5' Untranslated Regions
  • Guanine
  • Cytosine
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Adenine
  • Thymine