PMID- 19584085
OWN - NLM
STAT- MEDLINE
DCOM- 20091109
LR  - 20221207
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 18
IP  - 19
DP  - 2009 Oct 1
TI  - Identification of a new putative functional IL18 gene variant through an 
      association study in systemic lupus erythematosus.
PG  - 3739-48
LID - 10.1093/hmg/ddp301 [doi]
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role 
      in chronic inflammation and autoimmune disorders. In this study, we aimed to 
      determine the potential role of the IL18 gene in SLE. To define the genetic 
      association of the IL18 and SLE, we have genotyped nine SNPs in an independent 
      set of Spanish cases and controls. The IL18 polymorphisms were genotyped by PCR, 
      using a predeveloped TaqMan allele discrimination assay. Two SNPs were still 
      significant after fine mapping of the IL18 gene. The SNP (rs360719) surviving 
      correction for multiple tests was genotyped in two replication cohorts from Italy 
      and Argentina. After the analysis, a significance with rs360719 C-allele remained 
      across the sets and after the meta-analysis (Pooled OR = 1.37, 95% CI 1.21-1.54, 
      combined P = 3.8E-07, Pc = 1.16E-06). Quantitative real-time PCR was performed to 
      assess IL18 mRNA expression in PBMC from subjects with different IL18 rs360719 
      genotypes. We tested the effect of the IL18 rs360719 polymorphism on the 
      transcription of IL18 by electrophoretic mobility shift assay and western blot. 
      We found a significant increase in the relative expression of IL18 mRNA in 
      individuals carrying the rs360719 C-risk allele; in addition we show that the 
      polymorphism creates a binding site for the transcriptional factor OCT-1. These 
      findings suggest that the novel IL18 rs360719 variant may play an important role 
      in determining the susceptibility to SLE and it could be a key factor in the 
      expression of the IL18 gene.
FAU - Sanchez, Elena
AU  - Sanchez E
AD  - Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada 18100, Spain. 
      elena@ipb.csic.es
FAU - Palomino-Morales, Rogelio J
AU  - Palomino-Morales RJ
FAU - Ortego-Centeno, Norberto
AU  - Ortego-Centeno N
FAU - Jimenez-Alonso, Juan
AU  - Jimenez-Alonso J
FAU - Gonzalez-Gay, Miguel A
AU  - Gonzalez-Gay MA
FAU - Lopez-Nevot, Miguel A
AU  - Lopez-Nevot MA
FAU - Sanchez-Roman, Julio
AU  - Sanchez-Roman J
FAU - de Ramon, Enrique
AU  - de Ramon E
FAU - Gonzalez-Escribano, M Francisca
AU  - Gonzalez-Escribano MF
FAU - Pons-Estel, Bernardo A
AU  - Pons-Estel BA
FAU - D'Alfonso, Sandra
AU  - D'Alfonso S
FAU - Sebastiani, Gian Domenico
AU  - Sebastiani GD
CN  - Italian collaborative group
FAU - Alarcon-Riquelme, Marta E
AU  - Alarcon-Riquelme ME
FAU - Martin, Javier
AU  - Martin J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090707
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Case-Control Studies
MH  - Cell Line
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Gene Expression
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - *Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Interleukin-18/*genetics
MH  - Lupus Erythematosus, Systemic/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - White People/genetics
FIR - Barizzone, Nadia
IR  - Barizzone N
FIR - Galeazzi, Mauro
IR  - Galeazzi M
FIR - Danieli, Maria Giovanna
IR  - Danieli MG
FIR - Migliaresi, Sergio
IR  - Migliaresi S
FIR - Bozzolo, Enrica
IR  - Bozzolo E
EDAT- 2009/07/09 09:00
MHDA- 2009/11/10 06:00
CRDT- 2009/07/09 09:00
PHST- 2009/07/09 09:00 [entrez]
PHST- 2009/07/09 09:00 [pubmed]
PHST- 2009/11/10 06:00 [medline]
AID - ddp301 [pii]
AID - 10.1093/hmg/ddp301 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2009 Oct 1;18(19):3739-48. doi: 10.1093/hmg/ddp301. Epub 2009 Jul 
      7.