The dinucleotide (CA) repeat polymorphism of estrogen receptor beta but not the dinucleotide (TA) repeat polymorphism of estrogen receptor alpha is associated with venous ulceration

Ashworth, Jason J., Smyth, J. Vincent, Pendleton, Neil, Horan, Michael, Payton, Antony, Ollier, William E., Worthington, Jane and Ashcroft, Gillian S. (2005) The dinucleotide (CA) repeat polymorphism of estrogen receptor beta but not the dinucleotide (TA) repeat polymorphism of estrogen receptor alpha is associated with venous ulceration. The journal of steroid biochemistry and molecular biology, 97 (3). pp. 266-270. ISSN 0960-0760

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Abstract

Venous ulcers are the predominant form of chronic wound in the elderly, accounting for around 70% of all cases. The steroid sex hormone estrogen plays a crucial role in normal human skin maintenance and during cutaneous wound repair following injury. Estrogen can reverse age-related impaired wound healing by dampening the inflammatory response and increasing matrix deposition at the wound site. The molecular actions of estrogen are mediated through two nuclear sex steroid hormone receptors, estrogen receptor alpha (ERα) and beta (ERβ). We have conducted a case-control study to investigate whether dinucleotide repeat polymorphisms in the estrogen receptor genes are associated with venous ulceration in the UK Caucasian population. Genomic fragments containing the ERα dinucleotide (TA)n repeat polymorphism or the ERβ dinucleotide (CA)n repeat polymorphism were amplified by polymerase chain reaction in subject DNA samples and genotyped according to fragment length by capillary electrophoresis. There was no evidence to suggest that the TA repeat polymorphism of ERα was associated with venous ulceration. However, the CA*18 allele of the ERβ CA repeat polymorphism was significantly associated with venous ulceration (n = 120, OR = 1.8, 95% CI = 1.1–2.8, P = 0.02). When the CA repeats alleles were grouped together into either low (L ≤ 18) or high (H > 18) numbers of CA repeats, the low (L) repeat allele was significantly associated with venous ulceration (OR = 1.5, 95% CI = 1.0–2.2, P = 0.03). Our results show that a specific ERβ variant is associated with impaired healing in the elderly, predisposing individuals to venous ulceration.