T-786C polymorphism of the endothelial nitric oxide synthase gene and neuralgia-inducing cavitational osteonecrosis of the jaws.
OBJECTIVE
We hypothesized that, similar to idiopathic hip osteonecrosis, the T-786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with neuralgia-inducing cavitational osteonecrosis of the jaws (NICO).


METHODS
In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T-786C, stromelysin 5A6A) were measured by polymerase chain reaction. Two healthy normal control subjects were matched per case by race and gender.


RESULTS
Homozygosity for the mutant eNOS allele (TT) was present in 6 out of 22 patients (27%) with NICO compared with 0 out of 44 (0%) race and gender-matched control subjects; heterozygosity (TC) was present in 8 patients (36%) versus 15 control subjects (34%); and the wild-type normal genotype (CC) was present in 9 patients (36%) versus 29 controls (66%) (P = .0008). The mutant eNOS T-786C allele was more common in cases (20 out of 44 [45%]) than in control subjects (15 out of 88 [17%]) (P = .0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (P = .13).


CONCLUSIONS
The eNOS T-786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic medical approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO.
Glueck
Charles J
CJ
Cholesterol Center, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA. glueckch@healthall.com
McMahon
Robert E
RE
Bouquot
Jerry E
JE
Khan
Naseer A
NA
Wang
Ping
P
D000225:Adenine; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D003596:Cytosine; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007571:Jaw Diseases / Q000235:genetics*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D009437:Neuralgia / Q000209:etiology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010020:Osteonecrosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D013941:Thymine
D003596:Cytosine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019278:Matrix Metalloproteinase 3; D000225:Adenine; D013941:Thymine