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Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms.

ABSTRACT: The aim of this study was to examine the effect of hormone therapy and calcitriol on depression in older postmenopausal women and to determine whether the response was associated with polymorphisms of estrogen receptor ? and vitamin D receptor.In a double-blind placebo-controlled prospective trial involving 489 postmenopausal older women, a secondary analysis of depression was done. The Geriatric Depression Scale was used to screen for depression. We used binary logistic regression to examine the effect of treatment on depression and one-way analysis of variance to find a relationship between gene polymorphisms and depression.There was no effect of hormone therapy (odds ratio [OR], 1.65; 95% CI, 0.66-4.12; P = 0.277), calcitriol (OR, 1.15; 95% CI, 0.43-3.11; P = 0.772), or hormone therapy with calcitriol (OR, 1.01; 95% CI, 0.36-2.80; P = 0.979) on depression. Neither the polymorphisms of estrogen receptor ? (XbaI-? = 0.093; CI, -0.337 to 1.350; P = 0.239 and PvuII-? = -0.064; CI, -1.171 to 0.491, P = 0.421) nor those of vitamin D receptor (BsmI-? = 0.044, CI -2.546 to 3.030, P = 0.865 and TaqI-? = -0.015, CI -2.900 to 2.738, P = 0.955) were associated with depression.In older postmenopausal women, there was no effect of hormone therapy and calcitriol either individually or in combination with depression. Estrogen receptor ? and vitamin D receptor polymorphisms are not associated with depression or the response to intervention in older postmenopausal women. Additional trials are required to confirm these findings.

SUBMITTER: Yalamanchili V

PROVIDER: S-EPMC3319337 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms.

Yalamanchili Vinod V Gallagher J Christopher JC

Menopause (New York, N.Y.) 20120601 6

<h4>Objective</h4>The aim of this study was to examine the effect of hormone therapy and calcitriol on depression in older postmenopausal women and to determine whether the response was associated with polymorphisms of estrogen receptor α and vitamin D receptor.<h4>Methods</h4>In a double-blind placebo-controlled prospective trial involving 489 postmenopausal older women, a secondary analysis of depression was done. The Geriatric Depression Scale was used to screen for depression. We used binary ...[more]

PMID: 22205149

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Project description:IntroductionVitamin D receptor (VDR) genotypes may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D, but epidemiological studies have been inconsistent. Effect modification by serum 25-hydroxyvitamin D (25 [OH]D), the biomarker for vitamin D status in humans, has rarely been examined.MethodsWe assessed the effects of two frequently analyzed polymorphisms (FokI and TaqI) and two potentially functional variants (VDR-5132 and Cdx2) in the VDR gene, which thus far have not been analyzed with respect to breast cancer risk, on postmenopausal breast cancer risk in a population-based, case-control study including 1,408 patients (cases) and 2,612 control individuals (controls) matched for year of birth. Odds ratios (ORs) for breast cancer adjusted for potential confounders were calculated for genotypes and estimated haplotypes.ResultsNo differences in serum 25(OD)D concentrations by VDR genotype were observed. None of the analyzed polymorphisms was associated with overall risk for postmenopausal breast cancer. However, the TaqI polymorphism was associated with a significantly increased risk for oestrogen receptor positive tumours (OR = 1.18, 95% confidence interval [CI] = 1.00 to 1.38, comparing t allele carriers with noncarriers) but not for oestrogen receptor negative tumours (OR = 0.88, 95% CI = 0.69 to 1.13; P for interaction = 0.04). Haplotype analysis revealed the haplotype FtCA (FokI F, TaqI t, VDR-5132 C, Cdx2 A), which contains the TaqI t allele, to be associated with a significantly greater breast cancer risk as compared with the most frequent haplotype FTCG (OR = 1.43, 95% CI = 1.00 to 2.05). No significant interaction between VDR genotypes or haplotypes and 25(OH)D was observed.ConclusionOur results support potential effects of VDR polymorphisms on postmenopausal breast cancer risk and possible differential effects of receptor status of the tumour. However, further studies focusing on the influence of polymorphisms and haplotypes on VDR functionality, activity and concentration are needed.

Project description:BACKGROUND: The association between hormone treatment (HT) and mortality remains controversial. This study aimed to determine whether the risk of mortality associated with HT use varies depending on the specific characteristics of treatment and genetic variability in terms of the estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: A prospective, population-based study of 5135 women aged 65 years and older who were recruited from three cities in France and followed over six years. Detailed information related to HT use was obtained and five estrogen receptor polymorphisms were genotyped. The total follow-up was 25,436 person-years and during this time 352 women died. Cancer (36.4%) and cardiovascular disease (19.3%) were the major causes of death. Cox proportional hazards models adjusted for age, education, centre, living situation, comorbidity, depression, physical and mental incapacities, indicated no significant association between HT and mortality, regardless of the type or duration of treatment, or the age at initiation. However, the association between HT and all-cause or cancer-related mortality varied across women, with significant interactions identified with three estrogen receptor polymorphisms (p-values?=?0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1 rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI: 0.18-0.97), while in stark contrast, those homozygous for the T allele had a significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23-8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572. CONCLUSIONS/SIGNIFICANCE: The risk of mortality was not associated with HT duration, type or age at initiation. It was however not equal across all women, with some women appearing genetically more vulnerable to the effects of HT in terms of their estrogen receptor genotype. These findings, if confirmed in another independent study, may help explain the differential susceptibility of women to the beneficial or adverse effects of HT.

Project description:BackgroundGenome-wide association studies have identified several genomic regions that are associated with stroke risk, but these provide an explanation for only a small fraction of familial stroke aggregation. Genotype by environment interactions may contribute further to such an explanation. The Women's Health Initiative (WHI) clinical trial found increased stroke risk with postmenopausal hormone therapy (HT) and provides an efficient setting for evaluating genotype-HT interaction on stroke risk.MethodsWe examined HT by genotype interactions for 392 SNPs selected from candidate gene studies, and 2,371 SNPs associated with changes in blood protein concentrations after hormone therapy, in analyses that included 2,045 postmenopausal women who developed stroke during WHI clinical trial and observational study follow-up and one-to-one matched controls. A two-stage procedure was implemented where SNPs passing the first stage screening based on marginal association with stroke risk were tested in the second stage for interaction with HT using case-only analysis.ResultsThe two-stage procedure identified two SNPs, rs2154299 and rs12194855, in the coagulation factor XIII subunit A (F13A1) region and two SNPs, rs630431 and rs560892, in the proprotein convertase subtilisin kexin 9 (PCSK9) region, with an estimated false discovery rate <0.05 based on interaction tests. Further analyses showed significant stroke risk interaction between these F13A1 SNPs and estrogen plus progestin (E+P) treatment for ischemic stroke and for ischemic and hemorrhagic stroke combined, and suggested interactions between PCSK9 SNPs with either E+P or estrogen-alone treatment.ConclusionsGenotype by environment interaction information may help to define genomic regions relevant to stroke risk. Two-stage analysis among postmenopausal women generates novel hypotheses concerning the F13A1 and PCSK9 genomic regions and the effects of hormonal exposures on postmenopausal stroke risk for subsequent independent validation.

Dataset Information

Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms.

Publications

Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms.

Similar Datasets

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