» Articles » PMID: 30277919

The Association of an Alpha2C Adrenoreceptor Gene Polymorphism with Vasomotor Symptoms in African American Women

Overview
Journal Menopause
Date 2018 Oct 3
PMID 30277919
Authors
Affiliations
Soon will be listed here.
Abstract

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.

References
1.
Small K, Wagoner L, Levin A, Kardia S, Liggett S . Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure. N Engl J Med. 2002; 347(15):1135-42. DOI: 10.1056/NEJMoa020803. View

2.
Small K, Forbes S, Rahman F, Bridges K, Liggett S . A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors. J Biol Chem. 2000; 275(30):23059-64. DOI: 10.1074/jbc.M000796200. View

3.
Thurston R, Christie I, Matthews K . Hot flashes and cardiac vagal control: a link to cardiovascular risk?. Menopause. 2010; 17(3):456-61. PMC: 2866826. DOI: 10.1097/gme.0b013e3181c7dea7. View

4.
Link R, Stevens M, Kulatunga M, Scheinin M, Barsh G, Kobilka B . Targeted inactivation of the gene encoding the mouse alpha 2c-adrenoceptor homolog. Mol Pharmacol. 1995; 48(1):48-55. View

5.
Kardia S, Chu J, Sowers M . Characterizing variation in sex steroid hormone pathway genes in women of 4 races/ethnicities: the Study of Women's Health Across the Nation (SWAN). Am J Med. 2006; 119(9 Suppl 1):S3-15. DOI: 10.1016/j.amjmed.2006.07.001. View