Relation between renin-angiotensin-aldosterone system and otosclerosis: a genetic association and in vitro study.
OBJECTIVE
Angiotensin II (Ang II) may be implicated in the regulation of bone remodeling, and its activity is related to several gene polymorphisms including AGT M235T for plasmatic and tissular concentrations of angiotensinogen (AGT), ACE I/D for the angiotensin-converting enzyme activity, and AT(1)R A/C(1166) for the Ang II receptor function. The objective of this study was to investigate the implication of this hormone in otosclerosis.


METHODS
Prospective case-control study.


METHODS
The above-mentionedpolymorphisms were investigated in 186 patients with otosclerosis and 526 healthy controls, both groups originated from the French Caucasian population. Primary cell cultures of stapedial bone from patients with otosclerosis (n = 6) and control subjects (n = 5) were investigated for the messenger ribonucleic acid expressions of Ang II receptors (Types 1 and 2) and cellular AGT and the effect of Ang II (10(-7) mol/L, 24 h) on the alkaline phosphatase activity and the interleukin-6 secretion in the culture media.


RESULTS
A significant association was found between otosclerosis and the AGT M235T and the ACE I/D polymorphisms. Higher proportions of TT (29% versus 16%; p < 0.01) and DD (50% versus 38%; p < 0.05) genotypes were observed in cases versus controls. No association was found between the AT(1)R A/C(1166) polymorphism and otosclerosis. Ang II receptor Types 1 and 2 and AGT were detected in the cultures. Ang II increased the in vitro secretion of interleukin-6 and decreased the alkaline phosphatase activity only in otosclerotic cells.


CONCLUSIONS
These observations suggest a relation between the local renin angiotensin system activity and otosclerosis, opening new therapeutic insights.
Imauchi
Yutaka
Y
Unit-M 867, Institut de la santé et lde la recherche médicale, Faculté Xavier Bichat, Universite Paris, Paris, France.
Jeunemaître
Xavier
X
Boussion
Magali
M
Ferrary
Evelyne
E
Sterkers
Olivier
O
Grayeli
Alexis Bozorg
AB
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D008875:Middle Aged; D010040:Otosclerosis / Q000235:genetics* / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D013199:Stapes / Q000166:cytology / Q000502:physiology*
D015850:Interleukin-6; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; D000804:Angiotensin II; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A