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Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF‐ β /BMP pathway
Author(s) -
Nolan Vikki G.,
Adewoye Adeboye,
Baldwin Clinton,
Wang Ling,
Ma Qianli,
Wyszynski Diego F.,
Farrell John J.,
Sebastiani Paola,
Farrer Lindsay A.,
Steinberg Martin H.
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06074.x
Subject(s) - haemolysis , single nucleotide polymorphism , medicine , sickle cell anemia , endoglin , genotype , lactate dehydrogenase , ineffective erythropoiesis , biology , hemolytic anemia , immunology , endocrinology , anemia , gene , erythropoiesis , genetics , disease , stem cell , biochemistry , cd34 , enzyme
Summary Cutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. Sickle cell anaemia patients were studied to examine the relationship of leg ulcers with haemolysis and with single nucleotide polymorphisms (SNPs) in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate transaminase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age‐adjusted comparisons showed that sickle cell anaemia‐ α thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. 215 SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF‐ β /BMP signalling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial nitric oxide (NO) production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF‐ β /BMP signalling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis‐driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability.