Inhibitor kappa B-alpha (IkappaB-alpha) promoter polymorphisms in UK and Dutch sarcoidosis.
The aetiology of sarcoidosis is uncertain; current thinking implicates exposure of genetically susceptible hosts to environmental factors. The nuclear factor kappa B (NF-kappaB) family of transcription factors are critical regulators of immediate transcriptional responses in inflammatory situations and immune responses. Inhibitor kappa B-alpha (IkappaB-alpha) inhibits NF-kappaB and plays a major role in controlling its activity. We investigated IkappaB-alpha promoter polymorphisms using sequence-specific primer-polymerase chain reaction, at positions -881 (A/G), -826 (C/T), and -297 (C/T) in Caucasian sarcoidosis patients (UK and Dutch [NL]), each with their own controls. Disease severity at presentation was assigned using chest radiography and pulmonary function indices. In the combined populations, the -297T allele carriage was more prevalent in patients than in controls (P=0.008). Three common haplotypes were found, of which haplotype 2 (GTT) was significantly associated with sarcoidosis in comparison with control subjects (P=0.01). Subgroup analysis revealed that the -826T allelic carriage was most prevalent in stage II disease, and more prevalent in stage III than in stage IV (P=0.01). The -826T allelic carriage did not show any association with lung function. These results indicate that the NF-kappaB activation pathway might be associated with the inflammation of sarcoidosis.
Abdallah
A
A
Clinical Genomics Group, Royal Brompton Hospital, Imperial College, London, UK.
Sato
H
H
Grutters
J C
JC
Veeraraghavan
S
S
Lympany
P A
PA
Ruven
H J T
HJ
van den Bosch
J M M
JM
Wells
A U
AU
du Bois
R M
RM
Welsh
K I
KI
D018450:Disease Progression; D004198:Disease Susceptibility; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008168:Lung / Q000000981:diagnostic imaging; D000072000:NF-KappaB Inhibitor alpha; D009426:Netherlands; D011110:Polymorphism, Genetic; D011859:Radiography; D012129:Respiratory Function Tests; D017565:Sarcoidosis, Pulmonary / Q000000981:diagnostic imaging / Q000235:genetics*; D012720:Severity of Illness Index; D006113:United Kingdom
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha