Associations of the angiotensin II type 1 receptor A1166C and the endothelial NO synthase G894T gene polymorphisms with silent subcortical white matter lesions in essential hypertension.
OBJECTIVE
Silent white matter lesions (WMLs) may represent early target organ damage of the brain in patients with hypertension. Because these lesions may have a genetic background, we assessed the associations between polymorphisms of the renin-angiotensin system and the endothelial NO synthase (NOS3) genes and silent WMLs.


METHODS
Ninety-three hypertensive individuals were studied. MRI of the brain was performed to obtain estimates of the total volume of subcortical and the extent of periventricular WMLs. Patients were genotyped for the angiotensinogen (M235T), the angiotensin-converting enzyme (insertion/deletion [I/D]), the angiotensin II type 1 receptor (AGTR1 A1166C), and the NOS3 (G894T) genes. A linear regression model was used to assess the relationship of these gene polymorphisms with both subtypes of WMLs.


RESULTS
When adjusted for age, diabetes mellitus, and blood pressure, subcortical WML volume was lowest in the presence of 1 or 2 AGTR1 C alleles (unstandardized beta, -38.8 [95% CI, -66.1 to -11.4] and -112.6 [CI, -188.9 to -36.4], respectively), whereas it was highest in the presence of an NOS3 T allele (31.1[corrected] [CI, 3.6 to 58.4]). No interaction between these polymorphisms on WMLs could be demonstrated. No associations were present with the other polymorphisms, either with subcortical or periventricular lesions.


CONCLUSIONS
We found the AGTR1 A1166C as well as the NOS3 G894T polymorphisms to be associated with silent WMLs in the subcortical area.
Henskens
Léon H G
LH
Department of Internal Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Kroon
Abraham A
AA
van Boxtel
Martin P J
MP
Hofman
Paul A M
PA
de Leeuw
Peter W
PW
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics; D001794:Blood Pressure; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000235:genetics* / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A