The American Journal of Medicine
Volume 119, Issue 9, Supplement 1 , Pages S52-S60, September 2006

Vasomotor Symptom Prevalence Is Associated with Polymorphisms in Sex Steroid–Metabolizing Enzymes and Receptors

  • Carolyn J. Crandall, MD, MS

      Affiliations

    • Division of General Internal Medicine, Department of Medicine, University of California–Los Angeles, Los Angeles, California, USA
    • Corresponding Author InformationRequests for reprints should be addressed to Carolyn J. Crandall, MD, MS, Division of General Internal Medicine, Department of Medicine, University of California–Los Angeles, 911 Broxton Avenue, 1st Floor, Los Angeles, California 90024.
    • ,
  • Sybil L. Crawford, PhD

      Affiliations

    • Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    • ,
  • Ellen B. Gold, PhD

      Affiliations

    • Division of Epidemiology, Department of Public Health Sciences, University of California–Davis, Davis, California, USA

Abstract 

The relation of single nucleotide polymorphisms (SNPs) of genes involved in estrogen function to vasomotor symptoms (VMS) has been inadequately explored. We evaluated SNPs in sex steroid–metabolizing genes and estrogen receptors (ERs) for their association with VMS (hot flashes, night sweats, and/or cold sweats) reported by women who were premenopausal or in early perimenopause at baseline. The study population was drawn from participants in the Study of Women’s Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women, 42 to 52 years of age at baseline, who were enrolled in the longitudinal, community-based cohort of SWAN provided questionnaire, interview, weight and height measurements, and serum samples through the sixth annual visit. SNPs associated with the sex steroid hormone pathway were genotyped and available for 1,538 participants. These SNPs were associated with reporting VMS ≥6 days compared with <6 days in the past 2 weeks using race/ethnicity–specific repeated measures logistic regression models. Participants were on average 46 years old at baseline. The prevalence of VMS reporting increased in all racial/ethnic groups from baseline to the sixth annual follow-up visit. After adjustment for covariates, several SNPs encoding genes responsible for estrogen metabolism and ERs were associated with decreased odds of reporting VMS, including the CYP1B1 rs1056836 GC genotype in African American women; 17HSD rs615942 TG, 17HSD rs592389 TG, and 17HSD rs2830 AG genotypes in Caucasian women; and the CYP1A1 rs2606345 AC genotype in Chinese women. We identified race/ethnicity–specific associations between VMS reporting and specific polymorphisms for sex steroid–metabolizing enzymes and sex steroid receptors. Clarification of the mechanisms of the associations and confirmation in other populations is warranted.

Keywords:  Estrogen metabolism , Estrogen receptors , Genetics , Vasomotor symptoms , Women

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 The Study of Women’s Health Across the Nation (SWAN) and the SWAN Repository were supported by grants from the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health (Grant Nos. AG017719, NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). The Sex Steroid Hormone Genetics Protocol was supported by the SWAN Repository. Dr. Crandall was supported by National Institutes of Health Research Grant No. 5K12AG01004 from the National Institute on Aging.This report is based on samples from the SWAN DNA Repository. Scientists interested in developing studies based on this resource can find a description of the SWAN Core Repository and DNA Repository and information on obtaining access to the resources at www.swanrepository.org.

PII: S0002-9343(06)00829-1

doi:10.1016/j.amjmed.2006.07.007

The American Journal of Medicine
Volume 119, Issue 9, Supplement 1 , Pages S52-S60, September 2006

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