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

Molecular Psychiatry volume 15, pages 816–822 (2010)Cite this article

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.

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Acknowledgements

We acknowledge Denise Messer, MA for the development of the MR analysis method and image processing, and Carl Pieper, DrPh for guidance in statistical methods. This study was supported by NIMH Grants K23 MH65939, R01 MH54846, K24 MH70027 and P50 MH60451.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

    W D Taylor, D C Steffens, M E Payne & K R R Krishnan

  2. The Neuropsychiatric Imaging Research Laboratory, Duke University Medical Center, Durham, NC, USA

    W D Taylor, D C Steffens, M E Payne, J R MacFall & K R R Krishnan

  3. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    A Ashley-Koch & C F Potocky

  4. The Duke Center for Human Genetics, Duke University Medical Center, Durham, NC, USA

    A Ashley-Koch & C F Potocky

  5. Department of Radiology, Duke University Medical Center, Durham, NC, USA

    J R MacFall

  6. The Duke-NUS Graduate Medical School Singapore, Singapore

    K R R Krishnan

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  1. W D Taylor
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  2. D C Steffens
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  4. M E Payne
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Correspondence to W D Taylor.

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The authors declare no conflict of interest.

Additional information

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

Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Taylor, W., Steffens, D., Ashley-Koch, A. et al. Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men. Mol Psychiatry 15, 816–822 (2010). https://doi.org/10.1038/mp.2009.26

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