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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Article
On-Line Working Paper Series (2006)

Single nucleotide polymorphism (SNP) genotype frequencies were examined to determine whether variation in 6 estrogen-related genes was associated with differences in cognitive functioning in women at midlife. DNA from a multiracial/multiethnic sample of 875 African American, Caucasian, Chinese, and Japanese women aged 45 to 56 years participating in the Study of Women’s Health Across the Nation (SWAN) was genotyped. Gene markers from the sex steroid hormone pathway were linked to measures of cognitive functioning including the Digit Span Backward Test (DSB), a measure of working memory; the Symbol Digit Modalities Test (SDMT), a measure of perceptual speed; and the East Boston Memory Test (EBMT), a measure of episodic memory. Statistical models were fit using logistic regression and general linear models to estimate the strength of association of estrogen-related polymorphisms with DSB, SDMT, and EBMT scores. On the EBMT, African American women and Caucasian women with ESR1 rs9340799 GG genotypes had about 1.5 to 2.0 times greater odds of remembering story elements on the EBMT-immediate recall test. Caucasian women with ESR1 rs2234693 CC genotypes had 1.3 to 1.5 times greater odds of remembering story elements on the EBMTdelayed recall test. Chinese women with 17HSD rs615942 GG genotypes, 17HSD rs592389 TT genotypes, and 17HSD rs2830 GG genotypes had about 1.7 times greater odds of remembering story elements on the EBMT-immediate recall test. African American women with CYP 19 rs936306 CC genotypes had about 0.25 to 0.40 lower odds of remembering story elements on the EBMT-immediate recall test, whereas Chinese women with CYP 19 rs936306 CC genotypes had about 2.3 times greater odds of remembering story elements on both the EBMT-immediate and -delayed recall tests. On the DSB, African American women with CYP 19 rs749292 GG genotype had a higher mean score. On the SDMT, Japanese women with ESR1 rs728524 GG genotypes had a higher mean score. On the 3 tests of cognitive functioning, there was 1 significant finding for CYP1A1 and none for the YP1B1 or ESR2 SNPs. We conclude that selected genes involved in estrogen synthesis and metabolism may be associated with performance differences on cognitive function tests. Also, the relevant estrogen-related polymorphisms may vary by race/ethnicity.

    Cover page: Cognitive Functioning and Sex Steriod Hormone Gene Polymorphisms in Women at Midlife
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2013)

    Background

    Heart rate variability (HRV) differs markedly by race, yet few studies have evaluated these relationships in women, and none have done so during sleep (sHRV).

    Methods

    We addressed these gaps by examining sHRV in women of African American, Chinese American, or European American origin or descent (mean [standard deviation] age = 51.2 [2.2] years).

    Results

    HRV during Stage 2 non-rapid eye movement (NREM) and rapid eye movement (REM) sleep differed significantly by race after adjusting for possible confounders. Normalized high-frequency HRV was significantly lower in European American compared with African American and Chinese American participants (European American NREM = 0.35 [0.01], REM = 0.23 [0.01]; African American NREM = 0.43 [0.02], REM = 0.29 [0.02]; Chinese American NREM = 0.47 [0.03], REM = 0.33 [0.02]; p values <.001). European Americans also exhibited higher low-to-high-frequency HRV ratios during sleep compared with African American and Chinese American women (European American NREM = 2.42 [1.07], REM = 5.05 [1.07]; African American NREM = 1.69 [1.09], REM = 3.51 [1.09]; Chinese American NREM = 1.35 [1.07], REM = 2.88 [1.13]; p values <.001).

    Conclusions

    Race was robustly related to sHRV. Compared with women of African American or Chinese American origin or descent, European American women exhibited decreased vagally mediated control of the heart during sleep. Prospective data are needed to evaluate whether sHRV, including race differences, predicts cardiovascular disease.
      Cover page: Racial Differences in Heart Rate Variability During Sleep in Women
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2015)

      Objectives

      This research sought to assess racial and socioeconomic status (SES) differences in level and change in allostatic load (AL) over time in midlife women and to test whether psychosocial factors mediate these relationships. These factors were discrimination, perceived stress, and hostility.

      Methods

      Longitudinal data obtained from the Study of Women's Health Across the Nation were used (n = 2063; mean age at baseline = 46.0 years). Latent growth curve models evaluated the impact of demographic, menopausal, and psychosocial variables on level and change in AL for 8 years.

      Results

      Direct effects: high levels of discrimination and hostility significantly predicted higher AL (path coefficients = 0.05 and 0.05, respectively). High perceived stress significantly predicted a faster rate of increase of AL (path coefficient = 0.06). Racial and SES differentials were present, with African American race (path coefficient = 0.23), low income (path coefficient = -0.15), and low education (path coefficient = -0.08) significantly predicting high AL level. Indirect effects: significant indirect effects were found for African American race, less income, and lower education through higher discrimination, perceived stress, and hostility on level and rate of AL.

      Conclusions

      This was one of the first studies that investigated AL over multiple periods, and results supported AL as a cumulative phenomenon, affected by multiple psychosocial and demographic factors. The results suggest the complex ways in which race, SES, and psychosocial factors operate to influence AL.
        Cover page: A Longitudinal Investigation of Race, Socioeconomic Status, and Psychosocial Mediators of Allostatic Load in Midlife Women
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2021)

        Objective

        The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition.

        Study design

        SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy.

        Outcome measures

        We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C).

        Results

        A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood.

        Conclusion

        Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS.
          Cover page: Lowered progesterone metabolite excretion and a variable LH excretion pattern are associated with vasomotor symptoms but not negative mood in the early perimenopausal transition: Study of Women’s Health Across the Nation
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2015)

          Background

          Studies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain.

          Methods

          We examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women's Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein, fibrinogen, tissue-type plasminogen activator antigen, plasminogen activator inhibitor type 1, and factor VIIc (factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, 6-month, 1-month, and 1-day exposures and their relations to serum markers using longitudinal mixed models.

          Results

          For the 2,086 women studied from 1999 to 2004, PM2.5 exposures were associated with all blood markers except factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were strongest for prior year exposures for high-sensitivity C-reactive protein (21% increase per 10 μg/m³ PM2.5, 95% confidence interval [CI]: 6.6, 37), tissue-type plasminogen activator antigen (8.6%, 95% CI: 1.8, 16), and plasminogen activator inhibitor (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5).

          Conclusions

          Our findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women.
            Cover page: Long- and Short-term Exposure to Air Pollution and Inflammatory/Hemostatic Markers in Midlife Women
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2014)

            Background

            Several cohort studies report associations between chronic exposure to ambient fine particles (PM2.5) and cardiovascular mortality. Uncertainty exists about biological mechanisms responsible for this observation, but systemic inflammation has been postulated. In addition, the subgroups susceptible to inflammation have not been fully elucidated.

            Methods

            We investigated whether certain subgroups are susceptible to the effects of long-term exposure to PM2.5 on C-reactive protein (CRP), a marker of inflammation directly linked to subsequent cardiovascular disease. We used data from the SWAN cohort of 1923 mid-life women with up to five annual repeated measures of CRP. Linear mixed and GEE models accounting for repeated measurements within an individual were used to estimate the effects of prior-year PM2.5 exposure on CRP. We examined CRP as a continuous and as binary outcome for CRP greater than 3mg/l, a level of clinical significance.

            Results

            We found strong associations between PM2.5 and CRP among several subgroups. For example a 10 µg/m(3) increase in annual PM2.5 more than doubled the risk of CRP greater than 3mg/l in older diabetics, smokers and the unmarried. Larger effects were also observed among those with low income, high blood pressure, or who were using hormone therapy, with indications of a protective effects for those using statins or consuming moderate amounts of alcohol.

            Conclusions

            In this study, we observed significant associations between long-term exposure to PM2.5 and CRP in several susceptible subgroups. This suggests a plausible pathway by which exposure to particulate matter may be associated with increased risk of cardiovascular disease.
              Cover page: Chronic PM2.5 exposure and inflammation: Determining sensitive subgroups in mid-life women
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