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The association of an alpha2C adrenoreceptor gene polymorphism with vasomotor symptoms in African American women

Aharon, Devora A., MD1; Friedman, Elissa Gretz, MD1; Overbey, Jessica R., MS2; McLaughlin, Maryann, MD3; Langaee, Taimour, MSPH, PhD4; Thurston, Rebecca C., PhD5

doi: 10.1097/GME.0000000000001218
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Objective: The alpha2C adrenoreceptor deletion 322-325 (ADRA2C del 322-325) polymorphism has been associated with autonomic activity and thermoregulation, which are implicated in the vasomotor symptom (VMS) mechanism. The ADRA2C del (322-325) has higher prevalence in African American women, a group known to experience more frequent and bothersome VMS. We assessed whether the ADRA2C del (322-325) genotype is associated with increased frequency of VMS in African American women.

Methods: DNA samples from African American (N = 400) women participating in the Study of Women's Health Across the Nation (SWAN) were genotyped for the ADRA2C del (322-325) polymorphism. Longitudinal data on VMS were obtained from the SWAN repository. The relation of ADRA2C del (322-325) genotypes (deletion/deletion [D/D]; insertion/deletion [I/D]; insertion/insertion [I/I]) with VMS over the menopausal transition for up to 12 years of follow-up was examined using generalized estimating equations. Primary models considered the outcome of frequent VMS (6 or more days in the prior 2 wk vs VMS <6 d in the prior 2 wk) by stage of menopause.

Results: Four hundred DNA samples from African American women were included. Seventy-five women (18.8%) were found to carry the homozygous variant allele (D/D). There was no significant difference in the trajectory of frequent VMS over the menopausal transition between women with D/D and I/I + I/D genotypes (P = 0.39).

Conclusions: In this preliminary study among African American women in SWAN, ADRA2C del (322-325) was not significantly related to self-reported VMS. Further studies are warranted to help us understand the role of the adrenergic system in the physiology of VMS to tailor medical therapy to patient needs.

1Department of Obstetrics, Gynecology, and Reproductive Sciences, Icahn School of Medicine at Mount Sinai, New York, NY

2Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY

3Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY

4Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL

5Department of Psychiatry, Psychology, and Epidemiology, University of Pittsburgh, Pittsburgh, PA.

Address correspondence to: Devora A. Aharon, MD, Icahn School of Medicine at Mount Sinai, 1176 5th Avenue, Box 1170, New York, NY 10029. E-mail: Devora.Aharon@mountsinai.org

Received 5 July, 2018

Revised 27 August, 2018

Accepted 27 August, 2018

EGF is the co-first author.

Funding/support: The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH) (Grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, U01AG017719). This work was also supported by K24HL123565 (to Thurston). Department of Obstetrics, Gynecology and Reproductive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; NIH/NHLBI Grant # K24HL123565.

Financial disclosure/conflicts of interest: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, or the NIH.

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© 2019 by The North American Menopause Society.