Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men

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Molecular Psychiatry advance online publication 10 March 2009; doi: 10.1038/mp.2009.26

The preliminary data were presented at the 2008 Annual Meeting of the American Association for Geriatric Psychiatry in Orlando, Florida on 17 March 2008.

W D Taylor^1,2, D C Steffens^1,2, A Ashley-Koch^3,4, M E Payne^1,2, J R MacFall^5,2, C F Potocky^3,4 and K R R Krishnan^1,2,6

1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
2. The Neuropsychiatric Imaging Research Laboratory, Duke University Medical Center, Durham, NC, USA
3. Department of Medicine, Duke University Medical Center, Durham, NC, USA
4. The Duke Center for Human Genetics, Duke University Medical Center, Durham, NC, USA
5. Department of Radiology, Duke University Medical Center, Durham, NC, USA
6. The Duke-NUS Graduate Medical School Singapore, Singapore

Correspondence: Dr WD Taylor, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, DUMC Box 3903, Durham, NC 27710, USA. E-mail: Taylo066@mc.duke.edu

Received 20 October 2008; Revised 9 January 2009; Accepted 11 February 2009; Published online 10 March 2009.

Abstract

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, respectively. 137 depressed and 94 non-depressed participants aged 60 years were enrolled. Standard clinical evaluations were performed on all participants and blood samples obtained for genotyping. 1.5-T MRI (magnetic resonance imaging) data were obtained at baseline and approximately 2 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 were 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 (HTN) with the AGTR2 3123C allele exhibit less change in WML volume than hypertensive men with the 3123A allele, or men without HTN. 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 earlier observed gender differences of the relationship between other renin–angiotensin system polymorphisms and HTN. Further work is needed to determine whether these observed relationships are secondary to polymorphisms affecting response to antihypertensive medication, and whether antihypertensive medications can slow WML progression and lower the risk of morbidity associated with WMLs.