Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritis.
OBJECTIVE
To examine potential associations of the Glu/Asp(298) polymorphism in exon 7 and the 4a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility to and clinical expression of giant cell arteritis (GCA), particularly in patients with versus those without ischemic complications.


METHODS
Ninety-one consecutive patients with biopsy-proven GCA, who were residents of Reggio Emilia, Italy, and 133 population-based controls from the same geographic area were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and intron 4. The patients were separated into 2 subgroups according to the presence or absence of ischemic complications (visual loss and/or jaw claudication and/or aortic arch syndrome).


RESULTS
The distribution of the Glu/Asp(298) genotype differed significantly between GCA patients and controls (corrected P [P(corr)] = 0.003). Carriers of the Asp(298) allele (Asp/Asp or Glu/Asp) were significantly more frequent among the GCA patients than among the controls (P(corr) = 0.0002, odds ratio 3.3, 95% confidence interval 1.7-6.3). The distribution of the 4a/b genotype was similar in GCA patients and controls. No significant associations were found when GCA patients with and without ischemic complications were compared.


CONCLUSIONS
Our findings show that the Glu/Asp(298) polymorphism of the eNOS gene is associated with GCA susceptibility.
Salvarani
Carlo
C
Arcispedale S. Maria Nuova, Reggio Emilia, Italy. salvarani.carlo@asmn.re.it
Casali
Bruno
B
Nicoli
Davide
D
Farnetti
Enrico
E
Macchioni
Pierluigi
P
Catanoso
Maria Grazia
MG
Chen
Qingquan
Q
Bajocchi
GianLuigi
G
Boiardi
Luigi
L
D000368:Aged; D001224:Aspartic Acid; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013700:Giant Cell Arteritis / Q000201:enzymology* / Q000235:genetics; D018698:Glutamic Acid; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D001224:Aspartic Acid; D018698:Glutamic Acid; D004247:DNA; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III