The A1166C polymorphism of the AT1 receptor gene is associated with collagen type I synthesis and myocardial stiffness in hypertensives.
OBJECTIVE
We have investigated whether the A1166C polymorphism of the angiotensin II type 1 (AT1) receptor gene modulates the effects of angiotensin II on collagen type I turnover and myocardial stiffness in hypertension.


METHODS
We studied 255 hypertensive patients before and after 1 year of treatment with either losartan (n = 185) or atenolol (n = 70). Serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP) and the carboxy-terminal telopeptide of collagen type I (CITP), markers of extracellular collagen type I synthesis and degradation, respectively, were measured by specific radioimmunoassays. Left ventricular chamber stiffness (KLV), was determined from the deceleration time of the early mitral filling wave, as measured by Doppler echocardiography. Hypertensives were genotyped by polymerase chain reaction and divided in two subgroups: AA (n = 126) and AC/CC (n = 129).


RESULTS
Baseline PIP and KLV were increased (P < 0.01) in AA hypertensives compared with AC/CC hypertensives. No changes in baseline CITP were observed between the two subgroups of hypertensives. Confounding factors were similar between the two subgroups of hypertensives. Administration of losartan was associated with reduction (P < 0.01) in PIP and KLV in AA hypertensives but not in AC/CC hypertensives. Treatment with atenolol did not change PIP and KLV in either subgroup of hypertensives. No changes in CITP were observed with the two treatments.


CONCLUSIONS
These findings suggest that the A1166C polymorphism of the AT1 receptor gene is associated with collagen type I synthesis and myocardial stiffness in patients with hypertensive heart disease.
Division of Cardiovascular Pathophysiology, Centre for Applied Medical Research, School of Medicine, University of Navarra, Pamplona, Spain. jadimar@unav.es
Javier
J
Díez
Concepción
C
Laviades
Josune
J
Orbe
Guillermo
G
Zalba
Begoña
B
López
Arantxa
A
González
Gaspar
G
Mayor
José A
JA
Páramo
Oscar
O
Beloqui
D000225:Adenine; D000328:Adult; D000368:Aged; D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001262:Atenolol / Q000627:therapeutic use; D024042:Collagen Type I / Q000096:biosynthesis*; D003596:Cytosine; D004548:Elasticity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
D000959:Antihypertensive Agents; D024042:Collagen Type I; D044140:Receptor, Angiotensin, Type 1; D001262:Atenolol; D003596:Cytosine; D000225:Adenine; D019808:Losartan