Cytokine gene polymorphisms and high-resolution-computed tomography score in idiopathic pulmonary fibrosis.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown cause and the influence of cytokine gene polymorphisms is presumed in the etiology and pathogenesis of the disease. We used high-resolution computed tomography (HRCT) as a marker of disease stage and progression and compared the alveolar and interstitial score with IL-1, IL-4, IL-12, IL-1RA and IL-4RA cytokine gene polymorphisms.


METHODS
The IPF patients were all Caucasians from the Czech Republic and consisted of 20 females and 10 males, with a mean age of 65 years, range 36-85. The HRCT results were evaluated by an experienced viewer using the interstitial and alveolar score scales, which were based on the IPF HRCT description system from Gay SE, Kazerooni EA, Tows GB, Lynch JP, Gross BH, Cascade PN, et al. [Idiopathic pulmonary fibrosis. Predicting response to therapy and survival. Am J Respir Crit Care Med 1998;157:1063-72]. We evaluated the polymorphisms of cytokine genes utilizing a PCR with sequence-specific primers method.


RESULTS
The HRCT alveolar score was more pronounced in IL-4 RA (+1902) AG heterozygotes. The HRCT interstitial score was less severe in the IL-12 (-1188) AA homozygotes. According to progression of the HRCT interstitial score, the CC homozygosity at IL-1 RA (mspa 111100), the AA homozygosity at IL-4 RA (+1902) and CC homozygosity at IL-4(+33) positions were more frequent in patients with stable disease compared to those with progressive disease.


CONCLUSIONS
We assume from our data that the polymorphisms of IL-4, IL-4RA, IL-1RA and IL-12 genes (genes of cytokines with regulatory activity) might influence the phenotype of IPF as shown by measurable changes in HRCT investigations.
Vasakova
Martina
M
Department of Respiratory Diseases, 1st Medical School, Charles University, University Thomayer Hospital, Videnska 800, 140 59 Prague 4, Czech Republic. tichadohoda@volny.cz
Striz
Ilja
I
Dutka
Juraj
J
Slavcev
Antonij
A
Jandova
Sarka
S
Kolesar
Libor
L
Sulc
Jan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011650:Pulmonary Alveoli / Q000000981:diagnostic imaging; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000235:genetics*; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053662:Interleukin-4 Receptor alpha Subunit; D007378:Interleukins; D018664:Interleukin-12; D015847:Interleukin-4