PMID- 18070128
OWN - NLM
STAT- MEDLINE
DCOM- 20080229
LR  - 20161124
IS  - 1399-0004 (Electronic)
IS  - 0009-9163 (Linking)
VI  - 73
IP  - 1
DP  - 2008 Jan
TI  - Polymorphisms spanning the 0N exon and promoter of the estrogen receptor-beta 
      (ERbeta) gene ESR2 are associated with venous ulceration.
PG  - 55-61
AB  - Venous ulcers are characterized by excessive inflammation and raised levels of 
      proinflammatory cytokines. Estrogen has been shown to accelerate the rate of 
      wound healing in elderly subjects by dampening the inflammatory response. The 
      estrogen receptor (ER) proteins, ER-alpha (ERalpha) and ER-beta (ERbeta) mediate 
      the actions of estrogen during wound repair through the activation or repression 
      of target gene transcription. Recent evidence implicates the chromosomal region 
      harboring the ERbeta gene with venous ulceration in a British Caucasian 
      population, highlighting the need to conduct further genetic interrogation. To 
      address this, we conducted a case-control study to investigate whether single 
      nucleotide polymorphisms in the ERbeta gene are associated with venous ulceration 
      in elderly (age >50 years) subjects. We recruited a case group (n = 124, 56 males 
      and 68 females) consisting of patients with an active venous ulcer and a control 
      group consisting of individuals from the general population with no evidence of 
      venous disease or history of venous ulceration (n = 380, 189 males and 191 
      females). Polymorphisms in close proximity to upstream regulatory regions of the 
      ERbeta gene, including the 0N exon and promoter transcribed in inflammatory 
      cells, were significantly (p < 0.05) associated with venous ulceration. A major 
      susceptibility haplotype carried by 23% (26/112) of cases compared with only 10% 
      (27/276) of controls (odds ratio = 2.8, 95% confidence interval = 1.6-5.0) was 
      significantly (p < 0.01) associated with elevated serum levels of tumor necrosis 
      factor-alpha. In conclusion, common variation in the regulatory regions of the 
      ERbeta gene may pre-dispose to venous ulceration in a British Caucasian 
      population.
FAU - Ashworth, J J
AU  - Ashworth JJ
AD  - Department of Tissue Regeneration, Faculty of Life Sciences, University of 
      Manchester, Manchester, UK.
FAU - Smyth, J V
AU  - Smyth JV
FAU - Pendleton, N
AU  - Pendleton N
FAU - Horan, M
AU  - Horan M
FAU - Payton, A
AU  - Payton A
FAU - Worthington, J
AU  - Worthington J
FAU - Ollier, W E
AU  - Ollier WE
FAU - Ashcroft, G S
AU  - Ashcroft GS
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071129
PL  - Denmark
TA  - Clin Genet
JT  - Clinical genetics
JID - 0253664
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Estrogen Receptor beta/*genetics
MH  - *Exons
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Inflammation
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - *Promoter Regions, Genetic
MH  - Regulatory Sequences, Nucleic Acid
MH  - Tumor Necrosis Factor-alpha/blood
MH  - United Kingdom/epidemiology
MH  - Varicose Ulcer/*genetics
EDAT- 2007/12/12 09:00
MHDA- 2008/03/01 09:00
CRDT- 2007/12/12 09:00
PHST- 2007/12/12 09:00 [pubmed]
PHST- 2008/03/01 09:00 [medline]
PHST- 2007/12/12 09:00 [entrez]
AID - CGE927 [pii]
AID - 10.1111/j.1399-0004.2007.00927.x [doi]
PST - ppublish
SO  - Clin Genet. 2008 Jan;73(1):55-61. doi: 10.1111/j.1399-0004.2007.00927.x. Epub 
      2007 Nov 29.