Affiliation:
1. Academic Unit of Molecular Vascular Medicine, University of Leeds, Leeds General Infirmary, Leeds, U.K.
Abstract
Activation of the receptor for advanced glycation end products (RAGE) appears to be a key mechanism in the pathogenesis of diabetic vascular disease, making RAGE a candidate gene for investigation. RAGE is located in the major histocompatibility complex locus on chromosome 6, which contains a multitude of overlapping and duplicated genes involved predominantly in inflammatory and immune responses. The RAGE 5′ flanking region from −505 in a 5′ direction overlaps with PBX2, a gene that has a pseudogene copy on chromosome 3, making any studies of polymorphisms in this duplicated region potentially fraught with error. In this study we have addressed these issues by confirming RAGE as a predominantly single-copy gene and PBX2 to have two gene copies in the haploid human genome. We have characterized the gene:pseudogene differences between RAGE/PBX2 on chromosome 6 and ΨPBX2 on chromosome 3, which include a change from C to A at position −1139 RAGE/+2298 PBX2, previously reported as a polymorphism. Single chromosome–specific DNA amplification of the duplicated region has clarified five polymorphisms to be on chromosome 3 and one (at −1202 RAGE/+2234 PBX2) to be on chromosome 6. In conclusion, this study provides essential data for the study of RAGE and its genetics.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference16 articles.
1. Schmidt AM, Hori O, Brett J, Yan SD, Wautier JL, Stern D: Cellular receptors for advanced glycation end products: implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb 14:1521–1528, 1994
2. Schmidt AM, Stern D: RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes. Trends Endocrinol Metab 11:368–375, 2000
3. Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ, Chow WS, Stern D, Schmidt AM: Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 4:1025–1031, 1998
4. Soulis T, Thallas V, Youssef S, Gilbert RE, McWilliam BG, Murray-McIntosh RP, Cooper ME: Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury. Diabetologia 40:619–628, 1997
5. Ritthaler U, Deng Y, Zhang Y, Greten J, Abel M, Sido B, Allenberg J, Otto G, Roth H, Bierhaus A, Ziegler R, Schmidt AM, Waldherr R, Wahl P, Stern DM, Nawroth PP: Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease. Am J Pathol 146:688–694, 1995
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