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Structural analysis and evaluation of the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene in human essential hypertension

Brand, Eva1; Kato, Norihiro2; Chatelain, Nathalie1; Krozowski, Zygmunt S.3; Jeunemaitre, Xavier4; Corvol, Pierre4; Plouin, Pierre-François5; Cambien, François6; Pascoe, Leigh4,7; Soubrier, Florent1,8

Original article

Aim Mutations of the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive form of hypertension. We therefore investigated the question of whether variants of the 11β-HSD2 gene can contribute to genetic susceptibility to essential hypertension.

Subjects and methods We performed a linkage study in 162 French hypertensive sibships using the affected sib-pair method on 347 sibling pairs and a polymorphic microsatellite marker that we identified in a 30 kb cosmid clone containing the 11β-HSD2 gene. The coding sequence, introns 2–4 and 350 bp of the 5′-flanking region of the 11β-HSD2 gene were screened for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism, and a single polymorphism, Glu178/Glu (G534A), was identified in exon 3, which did not change the encoded amino acid sequence. A case–control study was conducted on 370 hypertensive subjects with a positive family history of hypertension and 783 French subjects with hypertension with or without a family history of hypertension, compared with 313 normotensive control subjects, all of whom were analyzed for the newly identified bi-allelic polymorphism.

Results Statistical analyses using the affected sib-pair method did not show significant linkage between the 11β-HSD2 microsatellite marker and hypertension. Furthermore, no positive association with hypertension was found with the Glu178/Glu (G534A) polymorphism.

Conclusion Our data do not suggest that variants of the 11β-HSD2 gene contribute substantially to essential hypertension in Caucasians.

1INSERM U358, Hôpital Saint-Louis, Paris, France

2Wellcome Trust Centre of Human Genetics, Oxford, UK

3Baker Institute of Medical Research, Prahran, Melbourne, Australia

4INSERM U36, Collège de France, Paris, France

5Hypertension Department, Hôpital Broussais, Paris, France

6INSERM SC7, Paris, France.

7Current address: Fondation Jean Dausset CEPH, Paris, France.

8Correspondence and requests for reprints to Dr Florent Soubrier, INSERM U358, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, F-75475 Paris, Cedex 10, France.

Tel: +33 1 5372 4015; fax: +33 1 5372 4020;


Sponsorship: This study was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG, Br 1589/1-1), the Société Française d'Hypertension Artérielle (E.B.), the Fondation Pour la Recherche Medicale, the IPSEN foundation for therapeutic research and the European Concerted Action (CT 94-1353, Molecular genetics of hypertension).

Received 2 June 1998 Revised 13 July 1998 Accepted 6 August 1998

© 1998 Lippincott Williams & Wilkins, Inc.