title: Polymorphism of the 5' untranslated region of NHE1 gene associated with type-I diabetes.
abstract: The ubiquitous form of the sodium-hydrogen exchanger, NHE1, is devoted to the regulation of intracellular pH and cell volume. In addition, NHE1 activity is stimulated by growth factors and increased NHE rates are found in both circulating and immortalized cells during diabetes or diabetic nephropathy. In this context, we searched for polymorphisms of the 5'-flanking regulatory region of NHE1 gene in subjects with type-I diabetes. We identified a C/T transition 696 bases upstream the translation initiation start site which disrupts a repeated palindromic GC sequence. The TT genotype was significantly more frequent in type-1 diabetics and may have functional importance. Genetic linkage between NHE1 and diabetes has been previously described in NOD mice strains with consequences on NHE rates. Hence, the polymorphism described hereby may act as a predisposition factor to type-I diabetes or to diabetic complications, and may be useful to investigate the genetic involvement of NHE1 in human pathophysiology.
authors.affiliation: Laboratoire de Biochimie III, Hôpital La Grave and INSERM Unité 326, IFR 30, Hôpital Purpan, France.
authors.forename: A
authors.initials: A
authors.lastname: Dubouix
authors.forename: I
authors.initials: I
authors.lastname: Gennero
authors.forename: M
authors.initials: M
authors.lastname: Niéto
authors.forename: N
authors.initials: N
authors.lastname: Ser
authors.forename: H
authors.initials: H
authors.lastname: Hannaire-Broutin
authors.forename: J P
authors.initials: JP
authors.lastname: Tauber
authors.forename: J
authors.initials: J
authors.lastname: Pourrat
authors.forename: J
authors.initials: J
authors.lastname: Fauvel
authors.forename: P
authors.initials: P
authors.lastname: Barthe
authors.forename: H
authors.initials: H
authors.lastname: Chap
authors.forename: J P
authors.initials: JP
authors.lastname: Salles
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D006801:Humans; D051379:Mice; D011110:Polymorphism, Genetic; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D017923:Sodium-Hydrogen Exchangers