Analysis of IL-12 p40 subunit gene and IFN-gamma G5644A polymorphisms in Idiopathic Pulmonary Fibrosis.
BACKGROUND
Genes encoding cytokine mediators are prime candidates for genetic analysis in conditions with T-helper (Th) cell disease driven imbalance. Idiopathic Pulmonary Fibrosis (IPF) is a predominantly Th2 mediated disease associated with a paucity of interferon-gamma (IFN-gamma). The paucity of IFN-gamma may favor the development of progressive fibrosis in IPF. Interleukin-12 (IL-12) plays a key role in inducing IFN-gamma production. The aim of the current study was to assess whether the 1188 (A/C) 3'UTR single nucleotide polymorphism (SNP) in the IL-12 p40 subunit gene which was recently found to be functional and the 5644 (G/A) 3' UTR SNP of the IFN-gamma gene were associated with susceptibility to IPF.


METHODS
We investigated the allelic distribution in these loci in UK white Caucasoid subjects comprising 73 patients with IPF and 157 healthy controls. The SNPs were determined using the polymerase chain reaction in association with sequence-specific primers incorporating mismatches at the 3'-end.


RESULTS
Our results showed that these polymorphisms were distributed similarly in the IPF and control groups


CONCLUSIONS
We conclude that these two potentially important candidate gene single nucleotide polymorphisms are not associated with susceptibility to IPF.
Latsi
Panagiota
P
Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College, National Heart and Lung Institute & Royal Brompton Hospital, London, United Kingdom. pepilats@hotmail.com <pepilats@hotmail.com>
Pantelidis
Panagiotis
P
Vassilakis
Dimitris
D
Sato
Hiroe
H
Welsh
Kenneth I
KI
du Bois
Roland M
RM
D020413:3' Untranslated Regions / Q000235:genetics*; D000225:Adenine; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006147:Guanine; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics*
D020413:3' Untranslated Regions; D017931:DNA Primers; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12; D006147:Guanine; D007371:Interferon-gamma; D000225:Adenine