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The Gene-Diet Associations in Postmenopausal Women with Newly Diagnosed Dyslipidemia.

ABSTRACT: OBJECTIVES:The aim of this study was to determine the relationship between polymorphisms of peroxisome proliferator activated receptor - PPAR gamma-2 (Pro12Ala, C1431T) and beta 3-adrenergic receptor - ADRB3 (Trp64Arg) and dietary habits in a group of postmenopausal women who were not under hypolipidemic treatment. DESIGN:Genetic, nutritional and anthropometric parameters were measured in 213 dyslipidemic (LDL ?115 mg/dL) and 58 normolipidemic (LDL<115) postmenopausal women. The PCR-RFLP method were used to determine the distributions of selected alleles and genotype frequencies. Dietary intake of basic components and fatty acids was obtained from a 7-day weighed food record and the bio-impedance method was used to determine nutritional status. RESULTS:Nearly 79% of analyzed women were in the first-time-diagnosed dyslipidemic state. The dyslipidemic subjects were characterized with higher intake of energy, fat, and saturated fatty acids (SFA). The analysis of the same polymorphisms showed association at the P value <0.05 with nutrients (fat, SFA, and polyunsaturated fatty acid - PUFA and saccharose) and elevated LDL level. Higher PUFA intake in a group of women with the protective Ala12/X polymorphism did not increase the risk of dyslipidemia even though they were characterized by visceral distribution of fat. The Arg64/X polymorphism and higher intake of energy, fat, and arachidic acid intake (C20:0) were associated with dyslipidemic state. CONCLUSION:Both nutritional and genetic factors are related to lipid profile. The identification of gene-diet associations is likely to provide useful information about the etiology of postmenopausal dyslipidemia and help in effective treatment.

SUBMITTER: Grygiel-Gorniak B

PROVIDER: S-EPMC5662705 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Gene-Diet Associations in Postmenopausal Women with Newly Diagnosed Dyslipidemia.

Grygiel-Górniak B B Kaczmarek E E Mosor M M Przysławski J J Nowak J J

The journal of nutrition, health & aging 20170101 9

<h4>Objectives</h4>The aim of this study was to determine the relationship between polymorphisms of peroxisome proliferator activated receptor - PPAR gamma-2 (Pro12Ala, C1431T) and beta 3-adrenergic receptor - ADRB3 (Trp64Arg) and dietary habits in a group of postmenopausal women who were not under hypolipidemic treatment.<h4>Design</h4>Genetic, nutritional and anthropometric parameters were measured in 213 dyslipidemic (LDL ≥115 mg/dL) and 58 normolipidemic (LDL<115) postmenopausal women. The P ...[more]

PMID: 29083445

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Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007

Project description:BackgroundNeurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by pro-inflammatory cytokines.MethodsOne hundred seventy-four postmenopausal patients with newly diagnosed breast cancer underwent a comprehensive neuropsychological evaluation (assessment of cognitive function, mood, and fatigue) and measurement of key cytokine levels prior to surgery. Age-matched control participants without cancer were evaluated concurrently. Multivariable regression analyses examined the contribution of circulating Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type two (sTNF-RII) in predicting neurocognitive performance in patients after controlling for key factors thought to impact functioning. All tests of statistical significance were two-sided.ResultsMemory performance was statistically significantly reduced, in patients compared with controls (P = .02). Of the three cytokines measured, only IL-1ra was statistically significantly elevated in cancer patients when compared with control participants (mean ± SD, 375 ± 239 pg/mL vs 291 ± 169 pg/mL, P = .007). After controlling for age, education, race, mood, fatigue, body mass index, and comorbidity, cytokines independently explained 6.0% of the total variance in memory performance (P = .01) in cancer patients but not control participants, with higher sTNF-RII associated with worse functioning. Exploratory analyses found that comorbidity statistically significantly explained variance in processing speed and executive functioning (P = .03 and P = .03, respectively).ConclusionAn association of TNF with memory, previously reported in patients after exposure to chemotherapy, was found prior to initiation of any treatment, including surgery. This association requires further investigation as sTNF-RII was not higher in cancer patients relative to control participants.

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The Gene-Diet Associations in Postmenopausal Women with Newly Diagnosed Dyslipidemia.

Publications

The Gene-Diet Associations in Postmenopausal Women with Newly Diagnosed Dyslipidemia.

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