PMID- 17845713
OWN - NLM
STAT- MEDLINE
DCOM- 20080408
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 9
IP  - 5
DP  - 2007
TI  - Association of the microsatellite in the 3' untranslated region of the CD154 gene 
      with rheumatoid arthritis in females from a Spanish cohort: a case-control study.
PG  - R89
AB  - CD40-CD154 interaction is an important mediator of inflammation and has been 
      implicated in T helper type 1-mediated autoimmune diseases including rheumatoid 
      arthritis (RA). Linkage studies have shown association of markers in the 
      proximity of the CD154 gene. In the present work we investigated whether specific 
      allele variants of the microsatellite in the 3' UTR of the CD154 gene might 
      modulate the risk of RA. The study, in a case-control setting, included 189 
      patients and 150 healthy controls from the Canary Islands, Spain. The 24CAs 
      allele was less represented in female patients than in controls (0.444 in 
      controls versus 0.307 in patients, P = 0.006, odds ratio (OR) 0.556, 95% 
      confidence interval (CI) 0.372 to 0.831) but not in males (0.414 versus 0.408), 
      and only when homozygous (P = 0.012; OR 0.35, 95% CI 0.16 to 0.77). We also 
      verified that CD154 association with RA was independent of human leukocyte 
      antigen (HLA) phenotype. A further functional study showed that after stimulation 
      anti-CD3, CD154 mRNA was more stable in CD4+ T lymphocytes from patients with RA 
      bearing the 24CAs allele (mRNA half-life 208 minutes) than in patients without 
      the 24CAs allele (109 minutes, P = 0.009). However, a lower percentage of 
      CD154+CD4+ T lymphocytes was seen in freshly isolated peripheral blood 
      mononuclear cells from patients carrying 24CAs alleles (mean 4.28 versus 8.12; P 
      = 0.033), and also in CD4+ T lymphocytes stimulated with anti-CD3 (median 29.40 
      versus 47.60; P = 0.025). These results were concordant with the smaller amounts 
      of CD154 mRNA isolated from stimulated T lymphocytes with 24CAs alleles. The 
      CD154 microsatellite therefore seems to affect the expression of the gene in a 
      complex manner that implies not only mRNA stability. These data suggest that the 
      CD154 microsatellite contributes to the regulation of mRNA and protein 
      expression, although further studies will be necessary to elucidate its role in 
      disease predisposition.
FAU - Martin-Donaire, Trinidad
AU  - Martin-Donaire T
AD  - Fundacion LAIR, Madrid, Spain. trini40l@hotmail.com
FAU - Losada-Fernandez, Ignacio
AU  - Losada-Fernandez I
FAU - Perez-Chacon, Gema
AU  - Perez-Chacon G
FAU - Rua-Figueroa, Inigo
AU  - Rua-Figueroa I
FAU - Erausquin, Celia
AU  - Erausquin C
FAU - Naranjo-Hernandez, Antonio
AU  - Naranjo-Hernandez A
FAU - Rosado, Silvia
AU  - Rosado S
FAU - Sanchez, Florentino
AU  - Sanchez F
FAU - Garcia-Saavedra, Ayoze
AU  - Garcia-Saavedra A
FAU - Citores, Maria Jesus
AU  - Citores MJ
FAU - Vargas, Juan A
AU  - Vargas JA
FAU - Perez-Aciego, Paloma
AU  - Perez-Aciego P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (3' Untranslated Regions)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - 3' Untranslated Regions/*genetics
MH  - Adult
MH  - *Alleles
MH  - Arthritis, Rheumatoid/epidemiology/*genetics
MH  - CD40 Ligand/*genetics
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats/*genetics
MH  - Middle Aged
MH  - Spain/epidemiology
PMC - PMC2212561
EDAT- 2007/09/12 09:00
MHDA- 2008/04/09 09:00
PMCR- 2007/09/10
CRDT- 2007/09/12 09:00
PHST- 2006/12/01 00:00 [received]
PHST- 2007/08/14 00:00 [revised]
PHST- 2007/09/10 00:00 [accepted]
PHST- 2007/09/12 09:00 [pubmed]
PHST- 2008/04/09 09:00 [medline]
PHST- 2007/09/12 09:00 [entrez]
PHST- 2007/09/10 00:00 [pmc-release]
AID - ar2288 [pii]
AID - 10.1186/ar2288 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2007;9(5):R89. doi: 10.1186/ar2288.