ANGIOTENSIN RECEPTOR GENE POLYMORPHISMS AND TWO-YEAR CHANGE IN HYPERINTENSE LESION VOLUME IN MEN

This longitudinal study examined the relationship between 2-year change in white matter hyperintense lesion (WML) volume and polymorphisms in genes coding for the angiotensin-II type 1 and type 2 receptors, AGTR1 A1166C and AGTR2 C3123A. 137 depressed and 94 nondepressed subjects age 60 years or older were enrolled. Standard clinical evaluations were performed on all subjects and blood samples obtained for genotyping. 1.5T MRI was obtained at baseline and approximately two years later. These scans were processed using a semi-automated segmentation process which allowed for the calculation of WML volume at each time point. Statistical models tested for the relationship between change in WML volume and genotype, while also controlling for age, sex, diagnostic strata, baseline WML volume, and comorbid cerebrovascular risk factors. In men, AGTR1 1166A allele homozygotes exhibited significantly less change in WML volume than 1166C carriers. We also found that men reporting hypertension with the AGTR2 3123C allele exhibit less change in WML volume than hypertensive men with the 3123A allele, or men without hypertension. There were no significant relationships between these polymorphisms and change in WML volume in women. No significant gene-gene or gene-depression interactions were observed. Our results parallel previously observed gender differences of the relationship between other renin-angiotensin system polymorphisms and hypertension. Further work is needed to determine if these observed relationships are secondary to polymorphisms affecting response to antihypertensive medication, and if antihypertensive medications can slow WML progression and lower the risk of morbidity associated with WMLs.